title: Serotonin (2C) receptor regulation of cocaine-induced conditioned place preference and locomotor sensitization.
abstract: Previous studies have identified an inhibitory regulatory role of the 5-HT(2C) receptor in serotonin and dopamine neurotransmission. As cocaine is known to enhance serotonin and dopamine transmission, the ability of 5-HT(2C) receptors to modulate cocaine-induced behaviors was investigated. Alterations in cocaine reward behavior were assessed in the conditioned place preference (CPP) paradigm. Mice were injected with a selective 5-HT(2C) receptor agonist, Ro 60-0175 (0, 1, 3, 10 mg/kg, i.p.) prior to cocaine administration (10 mg/kg, i.p.) on cocaine-conditioning days. Administration of Ro 60-0175(10 mg/kg) prior to cocaine attenuated the development of cocaine place preference. To assess the potential of the 5-HT(2C) receptor to influence cocaine-induced behavioral sensitization, mice were pretreated with either saline or Ro 60-0175 (10 mg/kg, i.p.) and 30 min later, administered cocaine (20 mg/kg, i.p.) or saline once daily for 5 days. Locomotor activity was measured daily following cocaine administration. After a 10-day drug-free period, locomotor activity was measured on day 16 following a challenge injection of cocaine (20 mg/kg, i.p.). Pharmacological activation of 5-HT(2C) receptors with Ro 60-0175 attenuated acute cocaine-induced activity on days 1-5, as well as the development of long-term cocaine-induced locomotor sensitization. Thus, activation of 5-HT(2C) receptors attenuated the rewarding and locomotor-stimulating effects of cocaine, as well as inhibited the development of sensitization. The current study shows that 5-HT(2C) receptor activity exerts an inhibitory influence on the short-term and long-term behavioral responses to cocaine.
authors.affiliation: Department of Pharmacologyand Center for Substance Abuse Research, Temple University School of Medicine, 3500N, Broad Street, Philadelphia, PA 19140, United States. caryne.craige@temple.edu
authors.forename: Caryne P
authors.initials: CP
authors.lastname: Craige
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Unterwald
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005021:Ethylamines / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology
chemical_list: D018765:Dopamine Uptake Inhibitors; D005021:Ethylamines; D007211:Indoles; D044405:Receptor, Serotonin, 5-HT2C; C103848:Ro 60-0175; D058826:Serotonin 5-HT2 Receptor Agonists; D003042:Cocaine