title: A 5-HT(2C) receptor antagonist potentiates a low dose amphetamine-induced conditioned place preference.
abstract: This study was designed to determine whether a 5-HT(2C) receptor antagonist could induce a conditioned place preference indicative of reward and/or abuse potential. Here, we present the first evidence that a selective 5-HT(2C) receptor antagonist, 6-chloro-5-ethoxy-N-(pyridin-2-yl)indoline-1-carboxamide hydrochloride (CEPC), can potentiate a low dose (0.5 mg/kg) amphetamine-induced positive conditioned place preference (CPP). CEPC did not produce any CPP given alone at doses of either 2.0 or 4.0 mg/kg, whereas low dose amphetamine alone produced only a slight, but statistically nonsignificant, place preference. These studies suggest that 5-HT(2C) receptor antagonists can indirectly potentiate the rewarding effects of amphetamine, and perhaps other psychostimulants. If the results can be translated to man, putative 5-HT(2C) receptor antagonist treatments for anxiety or depression may enhance or potentiate the rewarding effects of drugs of abuse such as amphetamine, which release dopamine.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: McCorvy
authors.forename: Aubrie A
authors.initials: AA
authors.lastname: Harland
authors.forename: Rebecca
authors.initials: R
authors.lastname: Maglathlin
authors.forename: David E
authors.initials: DE
authors.lastname: Nichols
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D000697:Central Nervous System Stimulants; D007211:Indoles; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D000661:Amphetamine