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Hyperlocomotive and discriminative stimulus effects of cocaine are under the control of serotonin(2C) (5-HT(2C)) receptors in rat prefrontal cortex.
J Pharmacol Exp Ther. 2003 Aug; 306(2):734-43.JP

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.

Authors+Show Affiliations

Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.No affiliation info available

Pub Type(s)

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.

Language

eng

PubMed ID

12721337

Citation

Filip, Malgorzata, and Kathryn A. Cunningham. "Hyperlocomotive and Discriminative Stimulus Effects of Cocaine Are Under the Control of serotonin(2C) (5-HT(2C)) Receptors in Rat Prefrontal Cortex." The Journal of Pharmacology and Experimental Therapeutics, vol. 306, no. 2, 2003, pp. 734-43.
Filip M, Cunningham KA. Hyperlocomotive and discriminative stimulus effects of cocaine are under the control of serotonin(2C) (5-HT(2C)) receptors in rat prefrontal cortex. J Pharmacol Exp Ther. 2003;306(2):734-43.
Filip, M., & Cunningham, K. A. (2003). Hyperlocomotive and discriminative stimulus effects of cocaine are under the control of serotonin(2C) (5-HT(2C)) receptors in rat prefrontal cortex. The Journal of Pharmacology and Experimental Therapeutics, 306(2), 734-43.
Filip M, Cunningham KA. Hyperlocomotive and Discriminative Stimulus Effects of Cocaine Are Under the Control of serotonin(2C) (5-HT(2C)) Receptors in Rat Prefrontal Cortex. J Pharmacol Exp Ther. 2003;306(2):734-43. PubMed PMID: 12721337.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hyperlocomotive and discriminative stimulus effects of cocaine are under the control of serotonin(2C) (5-HT(2C)) receptors in rat prefrontal cortex. AU - Filip,Malgorzata, AU - Cunningham,Kathryn A, Y1 - 2003/04/29/ PY - 2003/5/2/pubmed PY - 2003/8/29/medline PY - 2003/5/2/entrez SP - 734 EP - 43 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 306 IS - 2 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/12721337/Hyperlocomotive_and_discriminative_stimulus_effects_of_cocaine_are_under_the_control_of_serotonin_2C___5_HT_2C___receptors_in_rat_prefrontal_cortex_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12721337 DB - PRIME DP - Unbound Medicine ER -