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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.

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Department of Pharmacologyand Center for Substance Abuse Research, Temple University School of Medicine, 3500N, Broad Street, Philadelphia, PA 19140, United States.


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.

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