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Behav Brain Res. 2013 Feb 1;238:206-10. doi: 10.1016/j.bbr.2012.10.034. Epub 2012 Oct 26.

Serotonin (2C) receptor regulation of cocaine-induced conditioned place preference and locomotor sensitization.

Author information

1
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

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.

PMID:
23103406
PMCID:
PMC3513564
DOI:
10.1016/j.bbr.2012.10.034
[Indexed for MEDLINE]
Free PMC Article

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