Research article summary (published 27 Apr 2003):

Hyperlocomotive and discriminative stimulus effects of cocaine are under the control of serotonin(2C) (5-HT(2C)) receptors in rat prefrontal cortex.

Full Abstract

The serotonin2C (5-hydroxytryptamine2C; 5-HT2C) receptor (5-HT2CR) is found in abundance in dopamine (DA) mesocorticolimbic pathways and is one of the important target proteins that modulates the behavioral effects of cocaine. In the present study, the hypothesis was tested that the 5-HT2CR in the prefrontal cortex (PFC) may control either spontaneous or cocaine-evoked locomotor activity as well as the discriminative stimulus properties of cocaine. In male Sprague-Dawley rats implanted with bilateral cannulae aimed at the PFC, local microinjections of the preferential 5-HT2CR agonist 6-chloro-2-(1-piperazinyl)pyrazine hydrochloride (MK 212) (0.05-0.5 microg/side) did not alter spontaneous activity, but dose-dependently decreased horizontal hyperactivity evoked by cocaine (10 mg/kg i.p.). Given alone, the selective 5-HT2CR antagonist 8-[5-(2,4-dimethoxy-5-(4-trifluorophenylsulfonamido)phenyl-5-oxopentyl]-1,3,8-triazo-spiro[4.5]decane-2,4-dione hydrochloride (RS 102221) (5 microg/side) increased basal locomotor activity of rats expressed in the vertical plane. Microinjections of RS 102221 (5 microg/side, but not 0.15-1.5 microg/side) significantly enhanced the horizontal activity induced by cocaine (10 mg/kg). In rats trained to discriminate cocaine (10 mg/kg i.p.) from saline (i.p.) in a two-lever, water-reinforced fixed ratio 20 task, intra-PFC microinjections of MK 212 (0.05 and 0.5 microg/side) did not substitute for cocaine, but attenuated the stimulus effects of cocaine. However, intra-PFC microinjections of RS 102221 (1.5 and 5 microg/side) evoked 13 and 40% cocaine-lever responding when tested alone and enhanced the recognition of cocaine. These data indicate that the PFC is a brain site at which the 5-HT2CR exerts an inhibitory control over the hyperactive and discriminative stimulus effects of cocaine known to be dependent upon activation of the DA mesoaccumbens circuit.

Author information

Author/s: Filip, Malgorzata (M); Cunningham, Kathryn A (KA);

Affiliation: Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.

Grants: DA05708 (Agency:NIDA NIH HHS) ; DA06511 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.

Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther), published in United States. (Language: eng)

Reference: 2003-Aug; vol 306 (issue 2) : pp 734-43

Dates: Created 2003/07/21; Completed 2003/08/28; Revised 2007/11/14;

PMID: 12721337, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Cocaine - pharmacology Discrimination Learning - drug effects Dose-Response Relationship, Drug Male Microinjections Motor Activity - drug effects Prefrontal Cortex - drug effects; physiology Pyrazines - pharmacology

Rats Rats, Sprague-Dawley Receptor, Serotonin, 5-HT2C Receptors, Serotonin - physiology Serotonin Agonists - pharmacology Serotonin Antagonists - pharmacology Sodium Chloride - pharmacology Spiro Compounds - pharmacology Sulfonamides - pharmacology

Associated Chemicals: Pyrazines (0) ; RS 102221 (0) ; Receptor, Serotonin, 5-HT2C (0) ; Receptors, Serotonin (0) ; Serotonin Agonists (0) ; Serotonin Antagonists (0) ; Spiro Compounds (0) ; Sulfonamides (0) ; Cocaine (50-36-2) ; MK 212 (64022-27-1) ; Sodium Chloride (7647-14-5)

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