Neotic preferences in laboratory rodents: Issues, assessment and substrates

Neotic preference refers to the extent to which animals prefer stimuli of differing novelty value. Degree of novelty is determined by within- and between-trials habituation and amount of temporal (novelty) and spatial change (complexity) in stimulation which in turn will determine the amount of curiosity-based approach (neophilia) or fear-based avoidance (neophobia) of novel stimuli. Tests of genuine neotic preferences enable direct assessments of responsiveness to temporal and spatial changes and include measurements of novel versus familiar locations (such as novelty-related location preferences), responsiveness to stimulus complexity (such as object exploration) and learning for exploratory rewards (such as light-contingent bar-pressing). Effects of brain lesions and peripherally administered drugs have implicated several brain areas and neurotransmitters that subserve memory, fear and reward in neotic preferences namely the hippocampus and ACh (memory), the amygdala, GABA and 5-HT (fear), and the mesolimbic DA reward system. However, more attention should be paid to the complexity of interactions between different brain and neurotransmitter systems and improvements in methodology before conclusions should be drawn about the neurobiological basis of neotic preferences.

[1]  S. Glickman,et al.  BRAIN LESIONS AND LOCOMOTOR EXPLORATION IN THE ALBINO RAT. , 1964, Journal of comparative and physiological psychology.

[2]  J. D. McGaugh,et al.  Involvement of the amygdala in memory storage: interaction with other brain systems. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[3]  R. L. Moss,et al.  Olfactory lesions, emotionality and activity☆ , 1969 .

[4]  F. Mcsweeney,et al.  Habituation contributes to within-session changes in free wheel running. , 2001, Journal of the experimental analysis of behavior.

[5]  J. Platt,et al.  Response to stimulus change in the opossum. , 1967, The Journal of psychology.

[6]  M. J. Renner,et al.  Scopolamine suppresses both locomotion and object contact in a free-exploration situation , 1992, Pharmacology Biochemistry and Behavior.

[7]  S. Ikemoto,et al.  The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking , 1999, Brain Research Reviews.

[8]  R. Hughes,et al.  Treatment of adolescent rats with 1-benzylpiperazine: a preliminary study of subsequent behavioral effects. , 2006, Neurotoxicology and teratology.

[9]  J. Bizot,et al.  Effects of intraseptal infusions of N-methyl-d-aspartate receptor ligands on memory in an object recognition task in rats , 1998, Neuroscience Letters.

[10]  A. Kelley,et al.  Amphetamine, apomorphine and investigatory behavior in the rat: Analysis of the structure and pattern of responses , 2004, Psychopharmacology.

[11]  D. Amaral,et al.  Amygdalectomy and responsiveness to novelty in rhesus monkeys (Macaca mulatta): generality and individual consistency of effects. , 2006, Emotion.

[12]  P. Simon,et al.  Automatisation du test de la Planche à trous , 1967 .

[13]  R. Douglas,et al.  Spontaneous alternation and scopolamine , 1966 .

[14]  S. Iversen,et al.  Handbook of Psychopharmacology , 1988, Springer US.

[15]  R. Gerlai Behavioral tests of hippocampal function: simple paradigms complex problems , 2001, Behavioural Brain Research.

[16]  R. Butler Discrimination learning by rhesus monkeys to visual-exploration motivation. , 1953, Journal of comparative and physiological psychology.

[17]  桂木 猛 NEGLECTED FACTORS IN PHARMACOLOGY AND NEUROSCIENCE RESEARCH , 1995 .

[18]  G. Koob,et al.  Genetic Differences in Response to Novelty and Spatial Memory Using a Two-Trial Recognition Task in Mice , 2000, Neurobiology of Learning and Memory.

[19]  R. B. Lockard SOME EFFECTS OF LIGHT UPON THE BEHAVIOR OF RODENTS. , 1963, Psychological bulletin.

[20]  Peter H. Glow,et al.  Response-contingent sensory change in a causally structured environment , 1978 .

[21]  M. Thiébot Some evidence for amnesic-like effects of benzodiazepines in animals , 1985, Neuroscience & Biobehavioral Reviews.

[22]  J. Pratt,et al.  The neuroanatomical basis of anxiety. , 1992, Pharmacology & therapeutics.

[23]  R. Hughes Responsiveness to brightness change in hooded rats: effects of sex and procedure , 2001, Behavioural Processes.

[24]  H. Fibiger,et al.  On the role of the dorsal noradrenergic bundle in learning and habituation to novelty , 1988, Pharmacology Biochemistry and Behavior.

[25]  S. File Psychopharmacology of anxiolytics and antidepressants , 1991 .

[26]  P. Glow,et al.  Effects of dexamphetamine, amylobarbitone sodium and their mixture on sensory contingent bar pressing behaviour in the rat , 1973, Psychopharmacologia.

[27]  M. Wink,et al.  Exploration of environmental changes relates to lifestyle , 2005 .

[28]  M. Sarter,et al.  Attenuation of scopolamine-induced impairment of spontaneous alternation behaviour by antagonist but not inverse agonist and agonist β-carbolines , 2004, Psychopharmacology.

[29]  A. Mele,et al.  Involvement of glutamatergic and dopaminergic systems in the reactivity of mice to spatial and non-spatial change , 1996, Psychopharmacology.

[30]  R. Kirkby Exploratory Behavior in Rats following Bilateral Lesions of the Anterodorsal Caudate Nuclei , 1978, Perceptual and motor skills.

[31]  J. Brodkin Assessing memory in mice using habituation of nose-poke responding. , 1999, Behavioural pharmacology.

[32]  H. Takeda,et al.  Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. , 1998, European journal of pharmacology.

[33]  I. Lukaszewska,et al.  Response to stimulus change following observation or exploration by the rat: differential effects of hippocampal damages. , 1981, Acta neurobiologiae experimentalis.

[34]  J. S. Robinson The reinforcing effects of response-contingent light increment and decrement in hooded rats. , 1961, Journal of comparative and physiological psychology.

[35]  L. Squire Effects of pretrial and posttrial administration of cholinergic and anticholinergic drugs on spontaneous alternation. , 1969, Journal of comparative and physiological psychology.

[36]  Jonathan D. Cohen,et al.  Role of locus coeruleus in attention and behavioral flexibility , 1999, Biological Psychiatry.

[37]  K. Montgomery,et al.  The relation between fear induced by novel stimulation and exploratory behavior. , 1955, Journal of comparative and physiological psychology.

[38]  R. Hughes A review of atropinic drug effects on exploratory choice behavior in laboratory rodents. , 1982, Behavioral and neural biology.

[39]  R. Hughes Cholinergic and monoaminergic substrates of startle habituation. , 1984, Life sciences.

[40]  R. Bevins Novelty Seeking and Reward: Implications for the Study of High-Risk Behaviors , 2001 .

[41]  S. Irwin,et al.  Individual differences. I. Correlation between control locomotor activity and sensitivity to stimulant and depressant drugs. , 1958, The Journal of pharmacology and experimental therapeutics.

[42]  T. Robbins,et al.  A dissociation of the effects of d-amphetamine on locomotor activity and exploration in rats , 2004, Psychopharmacologia.

[43]  H. Harlow,et al.  Learning motivated by a manipulation drive. , 1950, Journal of experimental psychology.

[44]  A. Ennaceur,et al.  Detailed analysis of the behavior of Lister and Wistar rats in anxiety, object recognition and object location tasks , 2005, Behavioural Brain Research.

[45]  J. Gray The neuropsychology of anxiety. , 1985, Issues in mental health nursing.

[46]  R. F. Thompson,et al.  Habituation: a model phenomenon for the study of neuronal substrates of behavior. , 1966, Psychological review.

[47]  R. Hughes Chlordiazepoxide modified exploration in rats , 2004, Psychopharmacologia.

[48]  J. Delacour,et al.  A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data , 1988, Behavioural Brain Research.

[49]  A. Chocyk,et al.  Cortical localization of dopamine D4 receptors in the rat brain--immunocytochemical study. , 2000, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[50]  A. Phillips,et al.  Conditioned place preference as a measure of drug reward. , 1989 .

[51]  R N Walsh,et al.  The Open-Field Test: a critical review. , 1976, Psychological bulletin.

[52]  M. J. Renner,et al.  Age and sex as factors influencing spontaneous exploration and object investigation by preadult rats (Rattus norvegicus). , 1992, Journal of comparative psychology.

[53]  S. Hansen,et al.  Increased novelty seeking and decreased harm avoidance in rats showing Type 2-like behaviour following basal forebrain neuronal loss. , 2001, Alcohol and alcoholism.

[54]  R. L. Day,et al.  Neophilia, innovation and social learning: a study of intergeneric differences in callitrichid monkeys , 2003, Animal Behaviour.

[55]  W. Terry Habituation and dishabituation of rats’ exploration of a novel environment , 1979 .

[56]  R. Hughes,et al.  Prevention of memory loss for a brightness change in adult and middle-aged rats by postacquisition treatment with glucose , 2003, Pharmacology Biochemistry and Behavior.

[57]  M. Mauk,et al.  Buspirone attenuates synaptic activation of hippocampal pyramidal cells , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[58]  Trial-two goal arm alternation to orientation of trial-one starting stem , 1966 .

[59]  P. L. Carlton,et al.  7 – Behavioral Effects of Atropine and Scopolamine1 , 1971 .

[60]  R. Hughes Methylphenidate induced inhibition of exploratory behaviour in rats. , 1972, Life sciences. Pt. 1: Physiology and pharmacology.

[61]  R. O’connell COMPARISON OF ALTERNATION AND RESPONSE TO STIMULUS CHANGE. , 1964, Journal of Comparative and Physiological Psychology.

[62]  R. Hughes SPONTANEOUS ALTERNATION AND RESPONSE TO STIMULUS CHANGE IN THE FERRET. , 1965, Journal of comparative and physiological psychology.

[63]  D. Moncada,et al.  Phosphorylation state of CREB in the rat hippocampus: A molecular switch between spatial novelty and spatial familiarity? , 2006, Neurobiology of Learning and Memory.

[64]  M. Low,et al.  Dopamine D4 Receptor-Knock-Out Mice Exhibit Reduced Exploration of Novel Stimuli , 1999, The Journal of Neuroscience.

[65]  Joseph E LeDoux Emotion: clues from the brain. , 1995, Annual review of psychology.

[66]  P. Ropartz,et al.  Olfactory regulation of responsiveness to novelty in mice. , 1981, Behavioral and neural biology.

[67]  R. B. May Pretest exposure, changes in pattern complexity, and choice. , 1968, Journal of comparative and physiological psychology.

[68]  M. G. King,et al.  Uncertainty, as defined by the contingency between environmental events, and the adrenocortical response of the rat to electric shock. , 1977, Journal of comparative and physiological psychology.

[69]  Joseph E LeDoux,et al.  GABAergic Antagonists Block the Inhibitory Effects of Serotonin in the Lateral Amygdala: A Mechanism for Modulation of Sensory Inputs Related to Fear Conditioning , 1999, The Journal of Neuroscience.

[70]  S. Hansen,et al.  Links between temperamental dimensions and brain monoamines in the rat. , 2006, Behavioral neuroscience.

[71]  Effects of scopolamine and eserine on position discrimination learning with an exploratory incentive , 1968 .

[72]  L. Spear,et al.  Novel-object place conditioning in adolescent and adult male and female rats: effects of social isolation , 2003, Physiology & Behavior.

[73]  D. Mumby,et al.  Hippocampal damage and exploratory preferences in rats: memory for objects, places, and contexts. , 2002, Learning & memory.

[74]  T. Robbins,et al.  The Effects of Isolation-Rearing on Preference by Rats for A Novel Environment , 1997, Physiology & Behavior.

[75]  C. Gross,et al.  CURIOSITY IN THE HAMSTER. , 1965, Journal of comparative and physiological psychology.

[76]  M. McClintock,et al.  Fear of novelty in infant rats predicts adult corticosterone dynamics and an early death , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[77]  R. Hughes The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory , 2004, Neuroscience & Biobehavioral Reviews.

[78]  W. Paré,et al.  The emergence test: effects of psychotropic drugs on neophobic disposition in Wistar Kyoto (WKY) and Sprague Dawley Rats , 2001, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[79]  R. Pihl,et al.  The effect of dose, novelty, and exploration on amphetamine-produced stereotyped behavior , 1978, Psychopharmacology.

[80]  J. Harro Measurement of Exploratory Behavior in Rodents , 1993 .

[81]  R. Hughes,et al.  Intrinsic exploration in animals: motives and measurement , 1997, Behavioural Processes.

[82]  Stephen Maren,et al.  The effects of hippocampal lesions on two neotic choice tasks , 1993, Psychobiology.

[83]  J. Mellanby,et al.  The playground maze: a new method for measuring directed exploration in the rat , 1992, Journal of Neuroscience Methods.

[84]  G. Griebel,et al.  Comparison of the behavioural effects of an adenosine A1/A2-receptor antagonist, CGS 15943A, and an A1-selective antagonist, DPCPX , 2005, Psychopharmacology.

[85]  J. Bizot,et al.  Nicotine improves memory in an object recognition task in rats , 1999, European Neuropsychopharmacology.

[86]  R. Lister Ethologically-based animal models of anxiety disorders. , 1990, Pharmacology & therapeutics.

[87]  W. N. Dember,et al.  Analysis of exploratory, manipulatory, and curiosity behaviors. , 1957, Psychological review.

[88]  W. I. Welker,et al.  “Free” versus “Forced” Exploration of a Novel Situation by Rats , 1957 .

[89]  D. Berlyne,et al.  The arousal and satiation of perceptual curiosity in the rat. , 1955, Journal of comparative and physiological psychology.

[90]  J. Rawlins,et al.  Regional dissociations within the hippocampus—memory and anxiety , 2004, Neuroscience & Biobehavioral Reviews.

[91]  M. Bardo,et al.  Novelty-induced place preference behavior in rats: Effects of opiate and dopaminergic drugs , 1989, Pharmacology Biochemistry and Behavior.

[92]  E. Vesell GENETIC AND ENVIRONMENTAL FACTORS AFFECTING HEXOBARBITAL METABOLISM IN MICE , 1968, Annals of the New York Academy of Sciences.

[93]  R. Mccall,et al.  Differential rearing and the exploration of stimuli in the open field. , 1969 .

[94]  R. D. Walk Response of dark- and light-reared rats to stimulus change. , 1960, Journal of Comparative and Physiological Psychology.

[95]  R. Hughes Oxprenolol and diazepam effects on activity, novelty preference and timidity in rats. , 1981, Life sciences.

[96]  Henry W. Nissen,et al.  A Study of Exploratory Behavior in the White Rat by Means of the Obstruction Method , 1930 .

[97]  G Pepeu,et al.  Tacrine administration enhances extracellular acetylcholine in vivo and restores the cognitive impairment in aged rats. , 1997, Pharmacological research.

[98]  P. B. Singh,et al.  Chemosensation and genetic individuality. , 2001, Reproduction.

[99]  J. Archer,et al.  Exploration in animals and humans , 1983 .

[100]  R. Griffiths,et al.  The Role of Dopamine in the Behavioral Effects of Caffeine in Animals and Humans , 1997, Pharmacology Biochemistry and Behavior.

[101]  Michael T. Bardo,et al.  Conditioned increase in place preference by access to novel objects: antagonism by MK-801 , 1999, Behavioural Brain Research.

[102]  W. Thorpe Learning and instinct in animals , 1956 .

[103]  G. B. Kish Learning when the onset of illumination is used as reinforcing stimulus. , 1955, Journal of comparative and physiological psychology.

[104]  P. L. Carlton Brain acetylcholine and habituation. , 1968, Progress in brain research.

[105]  P. Ropartz,et al.  Effects of lateral amygdala lesions on the responses to novelty in mice , 1981, Behavioural Processes.

[106]  Robert Lalonde,et al.  The neurobiological basis of spontaneous alternation , 2002, Neuroscience & Biobehavioral Reviews.

[107]  F. Knowlton,et al.  Differential responses of coyotes to novel stimuli in familiar and unfamiliar settings , 2001 .

[108]  M. W. Brown,et al.  Novel spatial arrangements of familiar visual stimuli promote activity in the rat hippocampal formation but not the parahippocampal cortices: a c-fos expression study , 2004, Neuroscience.

[109]  C. Warden,et al.  Standard apparatus for the study of animal motivation. , 1926 .

[110]  Alice B. Sheldon Preference for familiar versus novel stimuli as a function of the familiarity of the environment. , 1969 .

[111]  P. Sanberg,et al.  Neuroscience and Biobehavioral Reviews , 2002, Physiology & Behavior.

[112]  M. Bardo,et al.  Effect of forebrain dopamine depletion on novelty-induced place preference behavior in rats , 1990, Pharmacology Biochemistry and Behavior.

[113]  E. Domino,et al.  THE EFFECT OF CHOLINERGIC BLOCKING DRUGS ON SPONTANEOUS ALTERNATION IN RATS. , 1964, Archives internationales de pharmacodynamie et de therapie.

[114]  S. File What can be learned from the effects of benzodiazepines on exploratory behavior? , 1985, Neuroscience & Biobehavioral Reviews.

[115]  Ann E. Kelley,et al.  Locomotor activity and exploration , 1993 .

[116]  H. Hurwitz Conditioned responses in rats reinforced by light , 1956 .

[117]  R. Hughes,et al.  Physostigmine effects on activity and reactions to novelty. , 1976, Life sciences.

[118]  D. Blanchard,et al.  Defensive reactions and exploratory behavior in rats. , 1974 .

[119]  W. N. Dember,et al.  Spontaneous alteration after free and forced trials. , 1959, Canadian journal of psychology.

[120]  J. Crawley Cholecystokinin accelerates the rate of habituation to a novel environment , 1984, Pharmacology Biochemistry and Behavior.

[121]  J. Siegel,et al.  Exploratory Behavior as a Function of Environmental Novelty and Complexity in Male and Female Rats , 2005, Psychological reports.

[122]  M. Hasselmo,et al.  Effect of long term baclofen treatment on recognition memory and novelty detection , 1996, Behavioural Brain Research.

[123]  L Stein,et al.  Benzodiazepines: Anxiety-Reducing Activity by Reduction of Serotonin Turnover in the Brain , 1972, Science.

[124]  M. Moser,et al.  Reduced fear expression after lesions of the ventral hippocampus , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[125]  Behavioral profile of the 5HT1A receptor antagonist (S)-UH-301 in rodents and monkeys , 1992, Brain Research Bulletin.

[126]  J. Harris,et al.  Habituatory response decrement in the intact organism. , 1943 .

[127]  R. Horsburgh,et al.  Modification of novelty preferences in rats by current and prior treatment with scopolamine and methylscopolamine , 2004, Psychopharmacology.

[128]  K. Montgomery The role of the exploratory drive in learning. , 1954, Journal of comparative and physiological psychology.

[129]  M. Geyer,et al.  RO-10-5824 is a selective dopamine D4 receptor agonist that increases novel object exploration in C57 mice , 2003, Neuropharmacology.

[130]  J. Becker Gender Differences in Dopaminergic Function in Striatum and Nucleus Accumbens , 1999, Pharmacology Biochemistry and Behavior.

[131]  B. Leonard Fundamentals of Psychopharmacology , 2003 .

[132]  E. Dere,et al.  Higher Order Memories for Objects Encountered in Different Spatio-temporal Contexts in Mice: Evidence for Episodic Memory , 2004, Reviews in the neurosciences.

[133]  R. Wise,et al.  Brain dopamine and reward. , 1989, Annual review of psychology.

[134]  E Save,et al.  Object exploration and reactions to spatial and nonspatial changes in hooded rats following damage to parietal cortex or hippocampal formation. , 1992, Behavioral neuroscience.

[135]  Robert N. Hughes Lack of spontaneous alternation in favor of perseveration in domestic fowls and pigeons , 1989, Behavioural Processes.

[136]  H. Fibiger,et al.  Evidence against a role of the rat's dorsal noradrenergic bundle in selective attention and place memory , 1983, Brain Research.

[137]  R. Hughes,et al.  Effects of methylphenidate on activity and reactions to novelty in rats , 1970 .

[138]  G. Griebel,et al.  Measuring normal and pathological anxiety-like behaviour in mice: a review , 2001, Behavioural Brain Research.

[139]  H. Schellinck,et al.  Odors of individuality of germfree mice are not discriminated by rats in a habituation- dishabituation procedure , 1995, Physiology & Behavior.

[140]  R. Lister,et al.  Does directed exploration influence locomotor activity in a holeboard test? , 1989, Behavioral and neural biology.

[141]  B. Anderson The volume of the cerebellar molecular layer predicts attention to novelty in rats , 1994, Brain Research.

[142]  V. Bolivar,et al.  Habituation in rodents: A review of behavior, neurobiology, and genetics , 2006, Neuroscience & Biobehavioral Reviews.

[143]  R. Bevins,et al.  Novelty reward as a measure of anhedonia , 2005, Neuroscience & Biobehavioral Reviews.

[144]  A. Becker,et al.  Kindling and its consequences on learning in rats. , 1992, Behavioral and neural biology.

[145]  W. Godwin Article in Press , 2000 .

[146]  K. Montgomery,et al.  Discrimination learning based upon the exploratory drive. , 1955, Journal of comparative and physiological psychology.

[147]  G. Griebel,et al.  The free‐exploratory paradigm: an effective method for measuring neophobic behaviour in mice and testing potential neophobia‐reducing drugs , 1993, Behavioural pharmacology.

[148]  D. Lester Sex Differences in Exploration: Toward a Theory of Exploration , 1967 .

[149]  H. Winkler,et al.  The significance of ecological factors for exploration and neophobia in parrots , 2002 .

[150]  R. Roesler,et al.  Pre- or post-training administration of the NMDA receptor blocker MK-801 impairs object recognition memory in rats , 2005, Behavioural Brain Research.

[151]  R. Hughes,et al.  Behaviour of male and female rats with free choice of two environments differing in novelty. , 1968, Animal behaviour.

[152]  W. Timberlake,et al.  Complexity, novelty, and food deprivation as determinants of speed of shift of behavior. , 1967, Journal of comparative and physiological psychology.

[153]  B. Slotnick,et al.  Changes in emotionality following destruction of the septal area in albino mice. , 1973, Brain, behavior and evolution.

[154]  R. Douglas,et al.  Spontaneous alternation and septal lesions. , 1966, Journal of comparative and physiological psychology.

[155]  E. Walker,et al.  Response to stimulus complexity in the Rat , 1964 .

[156]  J. Kamei,et al.  Effects of nociceptin on the exploratory behavior of mice in the hole-board test. , 2004, European journal of pharmacology.

[157]  P. E. Gold Acetylcholine modulation of neural systems involved in learning and memory , 2003, Neurobiology of Learning and Memory.

[158]  M. Bardo,et al.  Psychobiology of novelty seeking and drug seeking behavior , 1996, Behavioural Brain Research.

[159]  David C. Riccio,et al.  The Effects of a Target–stimulus Reminder on Performance in a Novel Object Recognition Task , 2003 .

[160]  W. Greenough,et al.  Memory consolidation : essays in honor of James L. McGaugh , 2001 .

[161]  P. L. Carlton,et al.  Pharmacological and anatomical dissociation of two types of habituation. , 1974, Journal of comparative and physiological psychology.

[162]  Sandra N. Moses,et al.  Differential involvement of amygdala and hippocampus in responding to novel objects and contexts , 2002, Brain Research Bulletin.

[163]  G. P. Smith,et al.  Decreased locomotor and investigatory exploration after denervation of catecholamine terminal fields in the forebrain of rats. , 1979, Journal of comparative and physiological psychology.

[164]  M. Hascöet,et al.  The mouse ligth-dark paradigm: A review , 2001, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[165]  T. Nakada,et al.  A Review of EEG and Blood Flow Data , 1998, Reviews in the neurosciences.

[166]  J. Mellanby,et al.  The effect of Ro 15-4513, an inverse agonist at the benzodiazepine receptor, on the exploratory response to novelty in the playground maze , 1994, Journal of psychopharmacology.

[167]  L. Huber,et al.  Social learning affects object exploration and manipulation in keas, Nestor notabilis , 2001, Animal Behaviour.

[168]  T. Robbins A Critique of the Methods Available for the Measurement of Spontaneous Motor Activity , 1977 .

[169]  B. Poucet,et al.  Scopolamine impairs response-to-change based on distal cues in the rat , 1989, Physiology & Behavior.

[170]  B. Berger Conditioning of food aversions by injections of psychoactive drugs. , 1972, Journal of comparative and physiological psychology.

[171]  J. Fritschy,et al.  A new benzodiazepine pharmacology. , 2002, The Journal of pharmacology and experimental therapeutics.

[172]  D. Berlyne,et al.  Motivational problems raised by exploratory and epistemic behavior. , 1962 .

[173]  A. Meneses,et al.  5-HT system and cognition , 1999, Neuroscience & Biobehavioral Reviews.

[174]  S. Lea Elements of a two-process theory of learning, J.A. Gray. Academic Press, London and New York (1975), x, + 423. Price £6·60/$16.50 , 1976 .

[175]  T. Kameyama,et al.  Behavioral evidence for a modulating role of σ ligands in memory processes. I. Attenuation of dizocilpine (MK-801)-induced amnesia , 1994, Brain Research.

[176]  B. Coffey Textbook of Pharmacotherapy for Child and Adolescent Psychiatric Disorders , 1996 .

[177]  D. Corey The determinants of exploration and neophobia , 1978, Neuroscience & Biobehavioral Reviews.

[178]  M. Buhot,et al.  Role of serotonin in memory impairment , 2000, Annals of medicine.

[179]  L. Sokoloff,et al.  Relationships among local functional activity, energy metabolism, and blood flow in the central nervous system. , 1981, Federation proceedings.

[180]  J. Mcgaugh,et al.  Facilitation of maze learning with posttrial injections of picrotoxin. , 1961, Journal of comparative and physiological psychology.

[181]  F. Sargolini,et al.  Effects of lesions to the glutamatergic afferents to the nucleus accumbens in the modulation of reactivity to spatial andnon-spatial novelty in mice , 1999, Neuroscience.

[182]  R. Bevins,et al.  The role of environmental familiarization in novel-object preference , 2000, Behavioural Processes.

[183]  J. Morley,et al.  Effect on memory processing by D-cycloserine, an agonist of the NMDA/glycine receptor. , 1992, European journal of pharmacology.

[184]  G. Loewenstein The psychology of curiosity: A review and reinterpretation. , 1994 .

[185]  R. N. Leaton EXPLORATORY BEHAVIOR IN RATS WITH HIPPOCAMPAL LESIONS. , 1965, Journal of comparative and physiological psychology.

[186]  C. Belzung,et al.  Interactions Between Dopamine and GABA in the Control of Ambulatory Activity and Neophobia in the Mouse , 1998, Pharmacology Biochemistry and Behavior.

[187]  R. Douglas The Development of Hippocampal Function: Implications for Theory and for Therapy , 1975 .

[188]  Harlow Hf Learning and satiation of response in intrinsically motivated complex puzzle performance by monkeys. , 1950 .

[189]  B. Meyers Some effects of scopolamine on a passive avoidance response in rats , 1965, Psychopharmacologia.

[190]  C. Messier Object Recognition in Mice: Improvement of Memory by Glucose , 1997, Neurobiology of Learning and Memory.

[191]  L. Buck,et al.  Information coding in the vertebrate olfactory system. , 1996, Annual review of neuroscience.

[192]  D. Williams,et al.  The effect of LSD-25 on light-reinforced behaviour in the rat , 2004, Psychopharmacologia.

[193]  M. Koch,et al.  The neurobiology of startle , 1999, Progress in Neurobiology.

[194]  Robert N. Hughes,et al.  Food deprivation and locomotor exploration in the white rat , 1965 .

[195]  M. J. Renner,et al.  Social interactions among rats housed in grouped and enriched conditions. , 1986, Developmental psychobiology.

[196]  R. Hughes Effects of adrenalin on novelty choices and activity in rats. , 1987, Life sciences.

[197]  M. Quirk,et al.  Requirement for Hippocampal CA3 NMDA Receptors in Associative Memory Recall , 2002, Science.

[198]  J. Knott The organization of behavior: A neuropsychological theory , 1951 .

[199]  Lithium chloride and avoidance of novel places. , 1983 .

[200]  R. Hughes,et al.  Cues used by male and female hooded rats for locating a brightness change , 2007, Behavioural Processes.

[201]  Locomotor activity and exploration: The use of traditional manipulators to dissociate these two behaviors in the rat , 1976 .

[202]  R. Hughes,et al.  Effects of food deprivation on exploration in deprivationally naive rats , 1970 .

[203]  T. Carew,et al.  Behavioral dissociation of dishabituation, sensitization, and inhibition in Aplysia. , 1988, Science.

[204]  A. Meneses Physiological, Pathophysiological and Therapeutic Roles of 5-HT Systems in Learning and Memory , 1998, Reviews in the neurosciences.

[205]  P Roullet,et al.  Nucleus accumbens dopamine receptors in the consolidation of spatial memory , 2004, Behavioural pharmacology.

[206]  C. Messier Glucose improvement of memory: a review. , 2004, European journal of pharmacology.

[207]  R. Hughes,et al.  Reactions of Ferret-Polecat Hybrids to Complexity and Change , 1968, Perceptual and motor skills.

[208]  G. Griebel,et al.  Serenics fluprazine (DU 27716) and eltoprazine (DU 28853) enhance neophobic and emotional behaviour in mice , 2005, Psychopharmacology.

[209]  R. Hughes,et al.  Chlordiazepoxide effects on reactions to novelty and activity with and without prior drug experience , 1975, Psychopharmacologia.

[210]  S. File,et al.  Validity of head-dipping as a measure of exploration in a modified hole-board , 1975, Psychopharmacologia.

[211]  R. Lister The amnesic action of benzodiazepines in man , 1985, Neuroscience & Biobehavioral Reviews.

[212]  T. Curran,et al.  Expression of c-fos protein in brain: metabolic mapping at the cellular level. , 1988, Science.

[213]  P. Salapatek,et al.  IS LIGHT INCREMENT REALLY REWARDING TO THE RAT? , 1964, Journal of comparative and physiological psychology.

[214]  W. N. Dember,et al.  Response by rats to differential stimulus complexity. , 1957, Journal of comparative and physiological psychology.

[215]  T. Wachs,et al.  Effects of arousing stimulation upon novelty preference in rats. , 1967, British journal of psychology.

[216]  P. Glow,et al.  Sound and light preference behaviour in naive adult rats , 1972 .

[217]  F. Sargolini,et al.  Role of dopaminergic system in reactivity to spatial and non-spatial changes in mice , 2000, Psychopharmacology.

[218]  G. B. Kish,et al.  Reinforcing properties of the onset of auditory stimulation. , 1961, Journal of experimental psychology.

[219]  R. Hughes Effects of physostigmine on novelty-related location preferences , 1992, Pharmacology Biochemistry and Behavior.

[220]  E. Azmitia,et al.  Age differences in within-session habituation of exploratory behavior: effects of stimulus complexity. , 1984, Behavioral and neural biology.

[221]  T. Robbins,et al.  Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal , 1983, Behavioural Brain Research.

[222]  Joseph P Huston,et al.  Episodic-like memory in mice: simultaneous assessment of object, place and temporal order memory. , 2005, Brain research. Brain research protocols.

[223]  R. Butler Incentive conditions which influence visual exploration. , 1954, Journal of experimental psychology.

[224]  B. Guardiola-Lemaitre,et al.  Effects of Melatonin on Neophobic Responses in Different Strains of Mice , 1999, Pharmacology Biochemistry and Behavior.

[225]  M. J. Renner Neglected aspects of exploratory and investigatory behavior , 1990, Psychobiology.

[226]  H. Viola,et al.  Detection of novelty, but not memory of spatial habituation, is associated with an increase in phosphorylated cAMP response element‐binding protein levels in the hippocampus , 2004, Hippocampus.

[227]  J. Vernikos,et al.  Plasma corticosterone concentrations sensitively reflect levels of stimulus intensity in the rat , 1979, Physiology & Behavior.

[228]  J. Tapp,et al.  Reinforcement and behavior , 1969 .

[229]  P. Russell,et al.  Relationships between exploratory behaviour and fear: a review. , 1973, British journal of psychology.

[230]  P. Ropartz,et al.  Effects of isolation, handling and novelty on the pituitary-adrenal response in the mouse , 1982, Psychoneuroendocrinology.

[231]  I. Izquierdo,et al.  Correlation between the Pharmacology of Long-Term Potentiation and the Pharmacology of Memory , 1995, Neurobiology of Learning and Memory.

[232]  R. Hughes,et al.  Sex-related Responsiveness to Changes in Tactile Stimulation in Hooded Rats , 2004 .

[233]  F. Holsboer,et al.  The modified hole board as a differential screen for behavior in rodents , 2001, Behavior research methods, instruments, & computers : a journal of the Psychonomic Society, Inc.

[234]  S. Sara,et al.  Locus coeruleus-evoked responses in behaving rats: A clue to the role of noradrenaline in memory , 1994, Brain Research Bulletin.

[235]  S. A. Barnett,et al.  Exploratory behaviour. , 1958, British journal of psychology.

[236]  P. Burghardt,et al.  Microinjection of Naltrexone into the Central, but not the Basolateral, Amygdala Blocks the Anxiolytic Effects of Diazepam in the Plus Maze , 2006, Neuropsychopharmacology.

[237]  M. Le Moal,et al.  Alternation behavior, spatial discrimination, and reversal disturbances following 6-hydroxydopamine lesions in the nucleus accumbens of the rat. , 1985, Behavioral and neural biology.

[238]  R. G. Dawson,et al.  Ontogenetic aspects of central cholinergic involvement in spontaneous alternation behavior. , 1973, Developmental psychobiology.

[239]  D. Berlyne A theory of human curiosity. , 1954, British journal of psychology.

[240]  O'connell Rh COMPARISON OF ALTERNATION AND RESPONSE TO STIMULUS CHANGE. , 1964 .

[241]  P. Ropartz,et al.  Impairment of responses to novelty by apomorphine and its antagonism by neuroleptics in mice , 1983, Psychopharmacology.

[242]  E. Kempf,et al.  Neurochemical lesion of the nucleus locus coeruleus increases neophobia in a specific exploration task but does not modify endocrine response to moderate stress , 1988, Pharmacology Biochemistry and Behavior.

[243]  C. Thiel,et al.  Hippocampal acetylcholine and habituation learning , 1998, Neuroscience.

[244]  R. Wimer,et al.  THE EFFECTS OF D-AMPHETAMINE SULPHATE ON THREE EXPLORATORY BEHAVIOURS. , 1965, Canadian journal of psychology.

[245]  I. Dedova,et al.  Behavioural effects of chronic haloperidol and risperidone treatment in rats , 2006, Behavioural Brain Research.

[246]  Frans van Haaren,et al.  Methods in behavioral pharmacology , 1993 .

[247]  H. Fowler,et al.  Response to Environmental Change: A Positive Replication , 1958 .

[248]  Anxiolytic effects of cytotoxic hippocampal lesions in rats. , 2002, Behavioral neuroscience.

[249]  R. Hughes Effects of glucose on responsiveness to change in young adult and middle-aged rats , 2003, Physiology & Behavior.

[250]  C. L. Richman,et al.  Olfactory cues and spontaneous alternation behavior , 1969 .

[251]  Shakti Sharma,et al.  The Effects of Early Rearing Environment on the Development of GABAA and Central Benzodiazepine Receptor Levels and Novelty-Induced Fearfulness in the Rat , 2000, Neuropsychopharmacology.

[252]  J. Aggleton,et al.  Spontaneous object recognition and object location memory in rats: the effects of lesions in the cingulate cortices, the medial prefrontal cortex, the cingulum bundle and the fornix , 1997, Experimental Brain Research.

[253]  C. Heyser,et al.  The Effects of Methylphenidate on Novel Object Exploration in Weanling and Periadolescent Rats , 2004, Annals of the New York Academy of Sciences.

[254]  T. Bussey,et al.  Removal of cholinergic input to perirhinal cortex disrupts object recognition but not spatial working memory in the rat , 2005, The European journal of neuroscience.

[255]  J. Gybels,et al.  Effects of electrical stimulation or lesion in nucleus accumbens on the behaviour of rats in a T-maze after administration of 8-OH-DPAT or vehicle , 2003, Behavioural Brain Research.

[256]  R. O’connell Spontaneous alternation and emotionality in rats with differential early experience , 1974 .

[257]  Rick A Bevins,et al.  Dopamine antagonism in a novel-object recognition and a novel-object place conditioning preparation with rats , 1999, Behavioural Brain Research.

[258]  C. Belzung,et al.  An investigation of the mechanisms responsible for acute fluoxetine‐induced anxiogenic‐like effects in mice , 2001, Behavioural pharmacology.

[259]  K. Montgomery,et al.  The relation between fear induced by novel stimulation and exploratory drive. , 1955 .

[260]  J. Gray,et al.  Emotionality in male and female rodents: a reply to Archer. , 1979, British journal of psychology.

[261]  Richard E. Brown Individual odors of rats are discriminable independently of changes in gonadal hormone levels , 1988, Physiology & Behavior.

[262]  R. Passingham,et al.  Syndrome produced by lesions of the amygdala in monkeys (Macaca mulatta). , 1981, Journal of comparative and physiological psychology.

[263]  P. L. Carlton,et al.  Ontogenetic dissociation of two classes of habituation. , 1975, Journal of comparative and physiological psychology.

[264]  M. Millan,et al.  The neurobiology and control of anxious states , 2003, Progress in Neurobiology.

[265]  R. Hughes,et al.  The role of social isolation and sex in determining effects of chlordiazepoxide and methylphenidate on exploratory behaviour , 2004, Psychopharmacologia.

[266]  C. Graf Effects of scopolamine on inhibitory mechanisms , 1974 .

[267]  E. Fehrer,et al.  The effects on hunger and familiarity of locale on exploration. , 1956, Journal of comparative and physiological psychology.

[268]  M. Geyer,et al.  A proposed animal model for hallucinogens based on LSD's effects on patterns of exploration in rats. , 1985, Behavioral neuroscience.

[269]  P. Ropartz,et al.  Effects of methamphetamine on novelty-seeking behaviour by mice , 2004, Psychopharmacology.

[270]  L. Squire,et al.  The medial temporal lobe memory system , 1991, Science.

[271]  S. A. Barnett,et al.  The new‐object and new‐place reactions of Rattus rattus L. , 1975 .

[272]  G. Sackett,et al.  Response to stimulus novelty and complexity as a function of rats' early rearing experiences. , 1967, Journal of comparative and physiological psychology.

[273]  K. Berridge,et al.  The Neuroscience of Natural Rewards: Relevance to Addictive Drugs , 2002, The Journal of Neuroscience.

[274]  R. Misslin,et al.  Reduction of neophobia in mice following lesions of the caudate-putamen , 1986, Physiology & Behavior.

[275]  P. Cowan,et al.  The new object reaction of Rattus rattus L: the relative importance of various cues. , 1976, Behavioral biology.

[276]  D. Amaral,et al.  The Amygdala, Social Behavior, and Danger Detection , 2003, Annals of the New York Academy of Sciences.

[277]  Exploratory Response of Rats to Stimuli of Differing Complexity , 1967, Perceptual and motor skills.

[278]  R. Mccall STIMULUS CHANGE IN LIGHT-CONTINGENT BAR PRESSING. , 1965, Journal of comparative and physiological psychology.

[279]  D. Berlyne,et al.  Perceptual curiosity exploratory behavior, and maze learning. , 1957, Journal of comparative and physiological psychology.

[280]  J. Gray,et al.  Précis of The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system , 1982, Behavioral and Brain Sciences.

[281]  R. Hughes Sex-related glucose effects on responsiveness to brightness change in middle-aged rats , 2002, Pharmacology Biochemistry and Behavior.

[282]  H. Fowler Curiosity and exploratory behavior , 1965 .

[283]  R. Butler,et al.  Daily patterns of visual exploratory behavior in the monkey. , 1955, Journal of comparative and physiological psychology.

[284]  M. Geyer,et al.  LSD-induced alterations of locomotor patterns and exploration in rats , 2004, Psychopharmacology.

[285]  R. Douglas Cues for spontaneous alternation. , 1966, Journal of comparative and physiological psychology.

[286]  W. N. Dember,et al.  Response by the rat to environmental change. , 1956, Journal of comparative and physiological psychology.

[287]  G. Aston-Jones,et al.  Discharge of noradrenergic locus coeruleus neurons in behaving rats and monkeys suggests a role in vigilance. , 1991, Progress in brain research.

[288]  R. Bevins,et al.  Novel-object place conditioning: behavioral and dopaminergic processes in expression of novelty reward , 2002, Behavioural Brain Research.

[289]  R. Hughes The role of self- and other-animal-produced odors in rats’ preferences for novelty in an exploration box , 1991, Psychobiology.

[290]  G. Moberg,et al.  Adrenocortical response to novelty stress in rats with dentate gyrus lesions. , 1980, Neuroendocrinology.

[291]  P. Cowan Neophobia and neophilia: New-object and new-place reactions of three Rattus species. , 1977 .

[292]  R. Hughes Memory-dependent novelty-related location preferences: Sex-related attenuation of forgetting by d-glucose and tacrine , 2006, Behavioural Brain Research.

[293]  L. Ahtee,et al.  The effect of benzodiazepines and atropine on exploratory behaviour and motor activity of mice , 1970, British journal of pharmacology.

[294]  W. N. Dember,et al.  Spontaneous alternation behavior. , 1958, Psychological bulletin.

[295]  Malcolm W. Brown,et al.  Different Contributions of the Hippocampus and Perirhinal Cortex to Recognition Memory , 1999, The Journal of Neuroscience.

[296]  J. Lisman,et al.  Storage, recall, and novelty detection of sequences by the hippocampus: Elaborating on the SOCRATIC model to account for normal and aberrant effects of dopamine , 2001, Hippocampus.

[297]  Joseph P. Huston,et al.  Wistar rats show episodic-like memory for unique experiences , 2006, Neurobiology of Learning and Memory.

[298]  W. Langhans,et al.  Enrichment-dependent differences in novelty exploration in rats can be explained by habituation , 2001, Behavioural Brain Research.

[299]  Leaton Rn Effects of scopolamine on exploratory motivated behavior. , 1968 .

[300]  Jonathan D. Cohen,et al.  Computational perspectives on dopamine function in prefrontal cortex , 2002, Current Opinion in Neurobiology.

[301]  Martin P Paulus,et al.  The balance between approach and avoidance behaviors in a novel object exploration paradigm in mice , 2004, Behavioural Brain Research.

[302]  Koch Sigmund Ed,et al.  Psychology: A Study of A Science , 1962 .

[303]  D. Berlyne NOVELTY AND CURIOSITY AS DETERMINANTS OF EXPLORATORY BEHAVIOUR1 , 1950 .

[304]  I. Lukaszewska Scopolamine affects response-to-change test involving 20-min retention interval after locomotor exploration in rats , 1993, Physiology & Behavior.

[305]  N. Miller,et al.  Failure to find a learned drive based on hunger; evidence for learning motivated by exploration. , 1954, Journal of comparative and physiological psychology.

[306]  S. Glickman,et al.  Curiosity in zoo animals. , 1966, Behaviour.

[307]  R. Hughes,et al.  Chronic imipramine effects on exploratory behavior in rats , 1987, Pharmacology Biochemistry and Behavior.

[308]  J. Packwood,et al.  Spontaneous alternation and D-amphetamine , 1969 .

[309]  P. Glow,et al.  Drug enhanced sensory contingent bar pressing: Comparing the effect of contingent and noncontingent sensory change , 1973, Psychopharmacologia.

[310]  J. L. Fobes,et al.  The central basis of motivation: intracranial self-stimulation studies. , 1981, Annual review of psychology.

[311]  P. Dudchenko An overview of the tasks used to test working memory in rodents , 2004, Neuroscience & Biobehavioral Reviews.

[312]  W. N. Dember,et al.  Spontaneous alternation behavior in animals: A review , 1986 .

[313]  J. Dalrymple-Alford Behavioral effects of basal forebrain grafts after dorsal septo-hippocampal pathway lesions , 1994, Brain Research.

[314]  D. Berlyne,et al.  Novelty, arousal, and the reinforcement of diversive exploration in the rat. , 1966, Journal of comparative and physiological psychology.

[315]  P. Glow,et al.  Sensory-contingent barpressing for familiar and novel change under a dexamphetamine-amylobarbitone mixture , 1974 .

[316]  R. Hughes,et al.  Effects of caffeine, methamphetamine and methylphenidate on reactions to novelty and activity in rats , 1976, Neuropharmacology.

[317]  G. Syme,et al.  The role of sex and novelty in determining the social response to lithium chloride , 2004, Psychopharmacologia.

[318]  R. C. Honey,et al.  Hippocampal Lesions Disrupt an Associative Mismatch Process , 1998, The Journal of Neuroscience.

[319]  R. Hughes Responsiveness to brightness change in male and female rats following treatment with the partial agonist of the N-methyl-d-aspartate receptor, d-cycloserine , 2004, Behavioural Brain Research.

[320]  P. Mcgeer,et al.  Localization and Possible Functions of Presenilins in Brain , 1998, Reviews in the neurosciences.

[321]  P. Ropartz,et al.  Responses to novelty and changes in behavior across a 3-week postoperative period in hippocampal-lesioned mice , 1981, Physiology & Behavior.

[322]  E. Furchtgott Pharmacological and biophysical agents and behavior , 1971 .

[323]  D. Levitsky,et al.  Lithium chloride and avoidance of novel places. , 1983, Behavioral neuroscience.

[324]  R. Hughes Effects of LSD on exploratory behavior and locomotion in rats. , 1973, Behavioral biology.

[325]  J. S. Cohen,et al.  Effect of deprivation level on exploratory behavior in the albino rat. , 1968, Journal of comparative and physiological psychology.