Modeling the effects of fluoxetine on food-reinforced behavior

We propose a novel method to dissociate incentive motivation from memory and motor processes in instrumental performance. Components of a multiple fixed-ratio schedule of food reinforcement were adjusted to envelop the range of response requirements that maintained lever pressing by rats. We sought to manipulate motivation for food rewards with acute administrations of various doses (0–10 mg/kg) of fluoxetine, a 5-HT reuptake inhibitor that reduces food intake. A quantitative model of fixed-ratio performance derived from Killeen's (1994) Mathematical Principles of Reinforcement (MPR) provided an adequate account of data from individual rats. Decreases in response rate resulting from fluoxetine were reflected in changes in estimates of activation, indexed by MPR parameter a; estimates of working memory capacity and lever pressing duration were not systematically affected. These results support the use of MPR parameter a to index incentive motivation using multiple fixed-ratio schedules that are adjusted to individual performance.

[1]  F. Ashby,et al.  The alicPrep statistic as a measure of confidence in model fitting , 2008, Psychonomic bulletin & review.

[2]  R. Hen,et al.  Chronic Blockade or Constitutive Deletion of the Serotonin Transporter Reduces Operant Responding for Food Reward , 2007, Neuropsychopharmacology.

[3]  M. Low,et al.  Differential involvement of endogenous opioids in sucrose consumption and food reinforcement , 2006, Pharmacology Biochemistry and Behavior.

[4]  Peter R Killeen,et al.  Chronic stress impairs spatial memory and motivation for reward without disrupting motor ability and motivation to explore. , 2006, Behavioral neuroscience.

[5]  J. Hensler,et al.  Fluoxetine disrupts food intake and estrous cyclicity in Fischer female rats , 2006, Brain Research.

[6]  C. Bradshaw,et al.  Quantitative analysis of the effects of some “atypical” and “conventional” antipsychotics on progressive ratio schedule performance , 2005, Psychopharmacology.

[7]  C. Bradshaw,et al.  Comparison of the effects of clozapine and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on progressive ratio schedule performance: evidence against the involvement of 5-HT1A receptors in the behavioural effects of clozapine , 2005, Psychopharmacology.

[8]  Joanne A Harrold,et al.  Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity. , 2005, Current drug targets.

[9]  J. Neisewander,et al.  Stimulation of 5-HT1B receptors decreases cocaine- and sucrose-seeking behavior , 2005, Pharmacology Biochemistry and Behavior.

[10]  C. M. Bradshaw,et al.  The effect of orbital prefrontal cortex lesions on performance on a progressive ratio schedule: implications for models of inter-temporal choice , 2005, Behavioural Brain Research.

[11]  J. Homberg,et al.  Individual differences in the effects of serotonergic anxiolytic drugs on the motivation to self-administer cocaine , 2004, Neuroscience.

[12]  Peter Dixon,et al.  Likelihood ratios: A simple and flexible statistic for empirical psychologists , 2004, Psychonomic bulletin & review.

[13]  Anne Lene Turi,et al.  Preclinical models of sexual desire: conceptual and behavioral analyses , 2004, Pharmacology Biochemistry and Behavior.

[14]  P. Currie,et al.  Sex differences in the reversal of fluoxetine-induced anorexia following raphe injections of 8-OH-DPAT , 2004, Psychopharmacology.

[15]  P. Fletcher,et al.  Fluoxetine, but not sertraline or citalopram, potentiates the locomotor stimulant effect of cocaine: possible pharmacokinetic effects , 2004, Psychopharmacology.

[16]  David R. Anderson,et al.  Model selection and multimodel inference : a practical information-theoretic approach , 2003 .

[17]  M. Reilly Extending mathematical principles of reinforcement into the domain of behavioral pharmacology , 2003, Behavioural Processes.

[18]  M. Ho,et al.  Effects of 8-OH-DPAT and WAY-100635 on performance on a time-constrained progressive-ratio schedule , 2003, Psychopharmacology.

[19]  J. Neisewander,et al.  Effects of fluoxetine and d-fenfluramine on cocaine-seeking behavior in rats , 2003, Psychopharmacology.

[20]  G. Gerhardt,et al.  Acute locomotor effects of fluoxetine, sertraline, and nomifensine in young versus aged Fischer 344 rats , 2002, Pharmacology Biochemistry and Behavior.

[21]  T. Kirkham,et al.  Reversal of Δ9-THC hyperphagia by SR141716 and naloxone but not dexfenfluramine , 2002, Pharmacology Biochemistry and Behavior.

[22]  L. Jarrard,et al.  The hippocampus and motivation revisited: appetite and activity , 2001, Behavioural Brain Research.

[23]  Thomas Steckler,et al.  Using signal detection methods for analysis of operant performance in mice , 2001, Behavioural Brain Research.

[24]  W K Bickel,et al.  Behavioral economics of human drug self‐administration: progressive ratio versus random sequences of response requirements , 2001, Behavioural pharmacology.

[25]  Lewis A. Bizo,et al.  Rats don’t always respond faster for more food: The paradoxical incentive effect , 2001 .

[26]  C. M. Bradshaw,et al.  Comparison of the effects of clozapine, haloperidol, chlorpromazine and d-amphetamine on performance on a time-constrained progressive ratio schedule and on locomotor behaviour in the rat , 2000, Psychopharmacology.

[27]  Trevor Sharp,et al.  A review of central 5-HT receptors and their function , 1999, Neuropharmacology.

[28]  J. Cantor,et al.  Chronic fluoxetine inhibits sexual behavior in the male rat: reversal with oxytocin , 1999, Psychopharmacology.

[29]  M. Lesage,et al.  Progressive-ratio schedules of drug delivery in the analysis of drug self-administration: a review , 1998, Psychopharmacology.

[30]  K. Larsson,et al.  The Selective Serotonin Reuptake Inhibitor Fluoxetine Reduces Sexual Motivation in Male Rats , 1998, Pharmacology Biochemistry and Behavior.

[31]  Rand R. Wilcox,et al.  How many discoveries have been lost by ignoring modern statistical methods , 1998 .

[32]  P R Killeen,et al.  Models of ratio schedule performance. , 1997, Journal of experimental psychology. Animal behavior processes.

[33]  D. Roberts,et al.  A Critique of Fixed and Progressive Ratio Schedules Used to Examine the Neural Substrates of Drug Reinforcement , 1997, Pharmacology Biochemistry and Behavior.

[34]  K. Simansky,et al.  Serotonergic control of the organization of feeding and satiety , 1995, Behavioural Brain Research.

[35]  G. Baker,et al.  Lesions of central serotonin systems affect responding on a progressive ratio schedule reinforced either by intravenous cocaine or by food , 1994, Pharmacology Biochemistry and Behavior.

[36]  P. Killeen Mathematical principles of reinforcement , 1994 .

[37]  Currie Pj,et al.  Diurnal variations in the feeding response to 8-OH-DPAT injected into the dorsal or median raphe. , 1993 .

[38]  P. Jacob,et al.  Fluoxetine for cocaine dependence in methadone maintenance: quantitative plasma and urine cocaine/benzoylecgonine concentrations. , 1993, Journal of clinical psychopharmacology.

[39]  Guy Mittleman,et al.  Reinforcer Magnitude and Progressive Ratio Responding in the Rat: Effects of Increased Effort, Prefeeding, and Extinction , 1993 .

[40]  F. M. Jacobsen,et al.  Fluoxetine-induced sexual dysfunction and an open trial of yohimbine. , 1992, The Journal of clinical psychiatry.

[41]  D. Wong,et al.  Fluoxetine, a selective inhibitor of serotonin uptake , 1991, Medicinal research reviews.

[42]  S. Hjorth,et al.  Application of brain microdialysis to study the pharmacology of the 5-HT1A autoreceptor , 1990, Journal of Neuroscience Methods.

[43]  M. Carroll,et al.  Fluoxetine reduces intravenous cocaine self-administration in rats , 1990, Pharmacology Biochemistry and Behavior.

[44]  S. Hjorth,et al.  The 5-HT1A receptor agonist, 8-OH-DPAT, preferentially activates cell body 5-HT autoreceptors in rat brain in vivo , 1988, Naunyn-Schmiedeberg's Archives of Pharmacology.

[45]  D. Wong,et al.  Suppression of food intake in rats by fluoxetine: Comparison of enantiomers and effects of serotonin antagonists , 1988, Pharmacology Biochemistry and Behavior.

[46]  S. Hanson,et al.  Arousal: its genesis and manifestation as response rate. , 1978, Psychological review.

[47]  R. Feldman,et al.  Chlordiazepoxide-fluoxetine interactions on food intake in free-feeding rats , 1978, Pharmacology Biochemistry and Behavior.

[48]  W HODOS,et al.  Progressive Ratio as a Measure of Reward Strength , 1961, Science.

[49]  W. Bickel,et al.  Replacing relative reinforcing efficacy with behavioral economic demand curves. , 2006, Journal of the experimental analysis of behavior.

[50]  J. Leander Fluoxetine suppresses palatability-induced ingestion , 2004, Psychopharmacology.

[51]  J. Ferguson The effects of antidepressants on sexual functioning in depressed patients: a review. , 2001, The Journal of clinical psychiatry.

[52]  R. Shrivastava,et al.  Reemergence of sexual dysfunction in patients with major depressive disorder: double-blind comparison of nefazodone and sertraline. , 2001, The Journal of clinical psychiatry.

[53]  Clive D. L. Wynne,et al.  Models of action : mechanisms for adaptive behavior , 1998 .

[54]  D. Coscina,et al.  Diurnal variations in the feeding response to 8-OH-DPAT injected into the dorsal or median raphe. , 1993, Neuroreport.

[55]  C. Dourish 5-HT RECEPTOR SUBTYPES AND FEEDING-BEHAVIOR , 1992 .

[56]  J. Rosenbaum,et al.  Fluoxetine treatment of cocaine abuse in heroin addicts. , 1991, The Journal of clinical psychiatry.

[57]  N. R. Richardson,et al.  Fluoxetine pretreatment reduces breaking points on a progressive ratio schedule reinforced by intravenous cocaine self-administration in the rat. , 1991, Life sciences.

[58]  P. Killeen On the temporal control of behavior. , 1975 .