Insights into the Neurobiology of Impulsive Behavior from Serotonin Receptor Knockout Mice

ABSTRACT: Although the concept of impulsivity has proved useful in human and animal studies of addiction, violent aggression, and violent suicide, and has been recognized as an important component of human behavior, little research has been done to understand the underlying psychobiological mechanisms. We explore the concept of impulsivity and its relation with the neurotransmitter serotonin in the context of aggressive behavior and behavior associated with positive reinforcement using a knockout mouse that lacks one of the serotonin receptors, the 5‐HT1B receptor. This knockou mouse shows more impulsive aggression, acquires cocaine self‐administration faster, and drinks more alcohol than the corresponding wild‐type control. We show that the impulsive characteristics of these mice are not due to change in cognitive functions: in a cognitive task involving a choice between a small immediate one and a larger more delayed reward, knockout mice showed intact choice and timing capabilities and good discrimination of reward amounts. Thus, this mouse may prove an animal model of addiction and motor impulsivity.

[1]  R. Hen,et al.  Increased vulnerability to cocaine in mice lacking the serotonin-1B receptor , 1998, Nature.

[2]  R. Hen,et al.  Intravenous Cocaine Self-Administration in Mice Lacking 5-HT1B Receptors , 1997, Pharmacology Biochemistry and Behavior.

[3]  R. Hen,et al.  5-Hydroxytryptamine1B receptors modulate the effect of cocaine on c-fos expression: converging evidence using 5-hydroxytryptamine1B knockout mice and the 5-hydroxytryptamine1B/1D antagonist GR127935. , 1997, Molecular pharmacology.

[4]  R. Hen,et al.  Elevated alcohol consumption in null mutant mice lacking 5–HT1B serotonin receptors , 1996, Nature Genetics.

[5]  J. Yamamoto Neurobiology of Violence , 1996 .

[6]  R. Hen,et al.  Mean Genes , 1996, Neuron.

[7]  J. Gibbon,et al.  Value of food aggregates: parallel versus serial discounting , 1995, Animal Behaviour.

[8]  R Hen,et al.  Enhanced aggressive behavior in mice lacking 5-HT1B receptor. , 1994, Science.

[9]  L. Green,et al.  Temporal discounting and preference reversals in choice between delayed outcomes , 1994, Psychonomic bulletin & review.

[10]  A. Caspi,et al.  Measuring impulsivity and examining its relationship to delinquency. , 1994, Journal of abnormal psychology.

[11]  M. Earleywine,et al.  Aggressivity, inattention, hyperactivity, and impulsivity in boys at high and low risk for substance abuse , 1994, Journal of abnormal child psychology.

[12]  M Linnoila,et al.  Brain serotonin, type II alcoholism and impulsive violence. , 1993, Journal of studies on alcohol. Supplement.

[13]  B. O'dowd,et al.  A single amino-acid difference confers major pharmacological variation between human and rodent 5-HT1B receptors , 1992, Nature.

[14]  Alex Kacelnik,et al.  Optimal foraging and timing processes in the starling, Sturnus vulgaris: effect of inter-capture interval , 1992, Animal Behaviour.

[15]  Michael J. Raleigh,et al.  Serotonergic mechanisms promote dominance acquisition in adult male vervet monkeys , 1991, Brain Research.

[16]  M. J. Kuhar,et al.  The dopamine hypothesis of the reinforcing properties of cocaine , 1991, Trends in Neurosciences.

[17]  S. Gleeson,et al.  5-HT1A agonist effects on punished responding of squirrel monkeys , 1990, Pharmacology Biochemistry and Behavior.

[18]  J. Palacios,et al.  5-HT1D receptors in the guinea pig brain: pre- and postsynaptic localizations in the striatonigral pathway , 1990, Brain Research.

[19]  H. Meltzer Role of Serotonin in Depression a , 1990, Annals of the New York Academy of Sciences.

[20]  A. Sjoerdsma,et al.  History of Serotonin and Serotonin Disorders , 1990, Annals of the New York Academy of Sciences.

[21]  B. Olivier,et al.  Ethopharmacological studies differentiate the effects of various serotonergic compounds on aggression in rats , 1990 .

[22]  T. Insel,et al.  Serotonergic modulation of rat pup ultrasonic vocal development: studies with 3,4-methylenedioxymethamphetamine. , 1990, The Journal of pharmacology and experimental therapeutics.

[23]  E. Coccaro Central Serotonin and Impulsive Aggression , 1989, British Journal of Psychiatry.

[24]  T. Beresford,et al.  Dopaminergic Activity of the Antimuscarinic Antiparkinsonian Agents , 1989, Journal of clinical psychopharmacology.

[25]  A. Logue Research on self-control: An integrating framework , 1988, Behavioral and Brain Sciences.

[26]  W. Schlenger,et al.  Acute and chronic effects of alcohol use on violence. , 1988, Journal of studies on alcohol.

[27]  B. Adinoff,et al.  Acting out hostility in normal volunteers: Negative correlation with levels of 5HIAA in cerebrospinal fluid , 1988, Psychiatry Research.

[28]  T. Manschreck,et al.  Characteristics of freebase cocaine psychosis. , 1988, The Yale journal of biology and medicine.

[29]  S. File,et al.  Selective agonists and antagonists for 5‐hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus‐maze test in the rat , 1987, The Journal of pharmacy and pharmacology.

[30]  W. Honer,et al.  PSYCHOSIS AND VIOLENCE IN COCAINE SMOKERS , 1987, The Lancet.

[31]  R M Church,et al.  Nutrients that modify the speed of internal clock and memory storage processes. , 1987, Behavioral neuroscience.

[32]  Cloninger Cr A systematic method for clinical description and classification of personality variants: A proposal. , 1987 .

[33]  P. Mandel,et al.  Inhibition of mouse killing behavior by serotonin-mimetic drugs: Effects of partial alterations of serotonin neurotransmission , 1987, Pharmacology Biochemistry and Behavior.

[34]  F. Goodwin,et al.  Cerebrospinal fluid monoamine metabolite levels in male arsonists. , 1987, Archives of general psychiatry.

[35]  Antoine Depaulis,et al.  Parachlorophenylalanine-induced serotonin depletion increases offensive but not defensive aggression in male rats , 1986, Physiology & Behavior.

[36]  P. Soubrié Reconciling the role of central serotonin neurons in human and animal behavior , 1986, Behavioral and Brain Sciences.

[37]  M. Thiébot Are serotonergic neurons involved in the control of anxiety and in the anxiolytic activity of benzodiazepines? , 1986, Pharmacology Biochemistry and Behavior.

[38]  J. Kagel,et al.  When foragers discount the future: constraint or adaptation? , 1986, Animal Behaviour.

[39]  S. Iversen 5-HT and anxiety , 1984, Neuropharmacology.

[40]  M Linnoila,et al.  Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. , 1983, Life sciences.

[41]  G. Koob,et al.  Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats , 1982, Pharmacology Biochemistry and Behavior.

[42]  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.

[43]  M. Strober,et al.  Validity of the Bulimia‐Restricter Distinction in Anorexia Nervosa Parental Personality Characteristics and Family Psychiatric Morbidity , 1982, The Journal of nervous and mental disease.

[44]  C. Robert Cloninger,et al.  Inheritance of alcohol abuse. Cross-fostering analysis of adopted men. , 1981, Archives of general psychiatry.

[45]  H. Moldofsky,et al.  The heterogeneity of anorexia nervosa. Bulimia as a distinct subgroup. , 1980, Archives of general psychiatry.

[46]  M. Humphreys,et al.  The interactive effect of personality, time of day, and caffeine: a test of the arousal model. , 1980, Journal of experimental psychology. General.

[47]  M. Humphreys,et al.  Individual differences in diurnal rhythms and multiple activation states: a reply to M. W. Eysenck and Folkard. , 1980, Journal of experimental psychology. General.

[48]  Barry L. Jacobs,et al.  Raphe unit activity in freely moving cats: Correlation with level of behavioral arousal , 1979, Brain Research.

[49]  A. Lippa,et al.  Use of DRL in differentiating anxiolytic and neuroleptic properties of CNS drugs , 1977, Pharmacology Biochemistry and Behavior.

[50]  G. Ainslie Specious reward: a behavioral theory of impulsiveness and impulse control. , 1975, Psychological bulletin.

[51]  P. Brain What does individual housing mean to a mouse? , 1975, Life sciences.

[52]  K. Lagerspetz,et al.  Changes in the aggressiveness of mice resulting from selective breeding, learning and social isolation. , 1971, Scandinavian journal of psychology.

[53]  A. W. Siegman The relationship between future time perspective, time. estimation, and impulse control in a group of young offenders and in a control group. , 1961, Journal of consulting psychology.

[54]  K. Maguire,et al.  Sourcebook of Criminal Justice Statistics: 1996 , 1996 .

[55]  C. Nemeroff,et al.  CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers. , 1994, Archives of general psychiatry.

[56]  T. Wills,et al.  Novelty seeking, risk taking, and related constructs as predictors of adolescent substance use: an application of Cloninger's theory. , 1994, Journal of substance abuse.

[57]  E. Hollander,et al.  Neurobiology of impulsivity and the impulse control disorders. , 1993, The Journal of neuropsychiatry and clinical neurosciences.

[58]  E. Barratt Impulsivity: Integrating cognitive, behavioral, biological, and environmental data. , 1993 .

[59]  S. Dickman,et al.  Impulsivity and information processing. , 1993 .

[60]  A. C. Collins,et al.  Animal models of alcoholism: genetic strategies and neurochemical mechanisms. , 1993, Biochemical Society symposium.

[61]  T. Branchek,et al.  A subfamily of 5-HT1D receptor genes. , 1992, Trends in pharmacological sciences.

[62]  George Loewenstein,et al.  The fall and rise of psychological explanations in the economics of intertemporal choice. , 1992 .

[63]  H. Berendsen,et al.  Pharmacology of Fear, Induced by Periaqueductal Gray Stimulation in the Rat , 1991 .

[64]  T. Insel,et al.  Are Glutamatergic Pathways Involved in the Pathophysiology of Anxiety , 1991 .

[65]  M. Linnoila,et al.  Serotonin in early onset, male alcoholics with violent behaviour. , 1990, Annals of medicine.

[66]  S. Brody Violence associated with acute cocaine use in patients admitted to a medical emergency department. , 1990, NIDA research monograph.

[67]  C. Robert Cloninger A systematic method for clinical description and classification of personality variants. A proposal. , 1987, Archives of general psychiatry.

[68]  B. Olivier A new anti-aggressive compound -- ethological studies , 1980 .

[69]  L. Valzelli,et al.  Brain tryptophan in isolated aggressive mice. , 1979, Neuropsychobiology.

[70]  K. Moyer The psychobiology of aggression , 1976 .