title: Decreased Incentive Motivation Following Knockout or Acute Blockade of the Serotonin Transporter: Role of the 5-HT2C Receptor.
abstract: Acute pharmacological elevation of serotonin (5-hydroxytryptamine; 5-HT) activity decreases operant responding for primary reinforcers, suggesting that 5-HT reduces incentive motivation. The mechanism by which 5-HT alters incentive motivation is unknown, but parallel evidence that 5-HT2C receptor agonists also reduce responding for primary reinforcers implicates this receptor as a potential candidate. These experiments examined whether chronic and acute disruptions of serotonin transporter (SERT) activity altered incentive motivation, and whether the 5-HT2C receptor mediated the effects of elevated 5-HT on behavior. To assess incentive motivation, we measured responding for three different reinforcers: a primary reinforcer (saccharin), a conditioned reinforcer (CRf), and an unconditioned sensory reinforcer (USRf). In the chronic condition, responding was compared between SERT knockout (SERT-KO) mice and their wild-type littermates. In the acute condition, responding was examined in wild-type mice following treatment with 10 or 20 mg/kg citalopram, or its vehicle. The ability of the selective 5-HT2C antagonist SB 242084 to prevent the effects of SERT-KO and citalopram on responding was subsequently examined. Both SERT-KO and citalopram reduced responding for saccharin, a CRf, and a USRf. Treatment with SB 242084 enhanced responding for a CRf and a USRf in SERT-KO mice and blocked the effects of citalopram on CRf and USRf responding. However, SB 242084 was unable to prevent the effects of SERT-KO or citalopram on responding for saccharin. These results support a powerful inhibitory function for 5-HT in the control of incentive motivation, and indicate that the 5-HT2C receptor mediates these effects of 5-HT in a reinforcer-dependent manner.
authors.affiliation: Department of Psychology, University of Toronto, Toronto, ON, Canada.|Section of Biopsychology, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON, Canada.
authors.forename: Caleb J
authors.initials: CJ
authors.lastname: Browne
authors.affiliation: Department of Psychology, University of Toronto, Toronto, ON, Canada.|Section of Biopsychology, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fletcher
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D015283:Citalopram / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009042:Motivation / Q000187:drug effects / Q000235:genetics*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012054:Reinforcement, Psychology; D012439:Saccharin / Q000008:administration & dosage; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013549:Sweetening Agents / Q000008:administration & dosage
chemical_list: D000631:Aminopyridines; D015283:Citalopram; D007211:Indoles; D044405:Receptor, Serotonin, 5-HT2C; D012439:Saccharin; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013549:Sweetening Agents; C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline