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Effects of 5-HT1B receptor ligands microinjected into the ventral tegmental area on cocaine discrimination in rats.
Eur J Pharmacol. 2003 Jan 17; 459(2-3):239-45.EJ

Abstract

Some recent data indicate a significant interaction between serotonin (5-hydroxytryptamine; 5-HT) and dopamine in mesolimbic brain structures (e.g. the ventral tegmental area) which modulate the behavioral effects of cocaine in rats. The present study investigated the role of 5-HT(1B) receptors in the ventral tegmental area in the discriminative stimulus effects of cocaine in rats. Male Wistar rats were trained to discriminate cocaine (10 mg/kg, intraperitoneally (i.p.)) from saline (i.p.) in a two-choice, water-reinforced fixed-ratio 20 procedure. After reaching the cocaine-saline discrimination criterion, the rats were stereotaxically implanted with bilateral cannulae in the ventral tegmental area and were then microinjected with selective 5-HT(1B) receptor ligands. In substitution studies, microinjections of the 5-HT(1B) receptor antagonist, 3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl]benzamide dihydrochloride (GR 55562; 0.1-1 microg/side), did not evoke cocaine-lever responding, whereas the 5-HT(1B) receptor agonist, 1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5H-pyrrolo[3,2-b]pyridin-5-one (CP 93129; 0.3-1 microg/side), induced partial substitution for cocaine. Intra-tegmental microinjections with the 5-HT(1B) receptor antagonist, GR 55562 (0.1-1 microg/side), before cocaine (5 mg/kg), which alone produced 98% cocaine-lever responses, decreased in a dose-dependent manner the discriminative stimulus effects of the psychostimulant. On the other hand, combination tests using a fixed dose of CP 93129 (0.3 or 1 microg/side), given into the ventral tegmental area prior to low systemic doses of cocaine (1.25-2.5 mg/kg), increased cocaine discrimination. These results seem to indicate that tegmental 5-HT(1B) receptors are necessary to express the discriminative stimulus effects of cocaine.

Authors+Show Affiliations

Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL-31-343, Cracow, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12524152

Citation

Filip, Małgorzata, et al. "Effects of 5-HT1B Receptor Ligands Microinjected Into the Ventral Tegmental Area On Cocaine Discrimination in Rats." European Journal of Pharmacology, vol. 459, no. 2-3, 2003, pp. 239-45.
Filip M, Papla I, Nowak E, et al. Effects of 5-HT1B receptor ligands microinjected into the ventral tegmental area on cocaine discrimination in rats. Eur J Pharmacol. 2003;459(2-3):239-45.
Filip, M., Papla, I., Nowak, E., Czepiel, K., & Przegaliński, E. (2003). Effects of 5-HT1B receptor ligands microinjected into the ventral tegmental area on cocaine discrimination in rats. European Journal of Pharmacology, 459(2-3), 239-45.
Filip M, et al. Effects of 5-HT1B Receptor Ligands Microinjected Into the Ventral Tegmental Area On Cocaine Discrimination in Rats. Eur J Pharmacol. 2003 Jan 17;459(2-3):239-45. PubMed PMID: 12524152.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of 5-HT1B receptor ligands microinjected into the ventral tegmental area on cocaine discrimination in rats. AU - Filip,Małgorzata, AU - Papla,Iwona, AU - Nowak,Ewa, AU - Czepiel,Klaudia, AU - Przegaliński,Edmund, PY - 2003/1/14/pubmed PY - 2003/8/26/medline PY - 2003/1/14/entrez SP - 239 EP - 45 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 459 IS - 2-3 N2 - Some recent data indicate a significant interaction between serotonin (5-hydroxytryptamine; 5-HT) and dopamine in mesolimbic brain structures (e.g. the ventral tegmental area) which modulate the behavioral effects of cocaine in rats. The present study investigated the role of 5-HT(1B) receptors in the ventral tegmental area in the discriminative stimulus effects of cocaine in rats. Male Wistar rats were trained to discriminate cocaine (10 mg/kg, intraperitoneally (i.p.)) from saline (i.p.) in a two-choice, water-reinforced fixed-ratio 20 procedure. After reaching the cocaine-saline discrimination criterion, the rats were stereotaxically implanted with bilateral cannulae in the ventral tegmental area and were then microinjected with selective 5-HT(1B) receptor ligands. In substitution studies, microinjections of the 5-HT(1B) receptor antagonist, 3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl]benzamide dihydrochloride (GR 55562; 0.1-1 microg/side), did not evoke cocaine-lever responding, whereas the 5-HT(1B) receptor agonist, 1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5H-pyrrolo[3,2-b]pyridin-5-one (CP 93129; 0.3-1 microg/side), induced partial substitution for cocaine. Intra-tegmental microinjections with the 5-HT(1B) receptor antagonist, GR 55562 (0.1-1 microg/side), before cocaine (5 mg/kg), which alone produced 98% cocaine-lever responses, decreased in a dose-dependent manner the discriminative stimulus effects of the psychostimulant. On the other hand, combination tests using a fixed dose of CP 93129 (0.3 or 1 microg/side), given into the ventral tegmental area prior to low systemic doses of cocaine (1.25-2.5 mg/kg), increased cocaine discrimination. These results seem to indicate that tegmental 5-HT(1B) receptors are necessary to express the discriminative stimulus effects of cocaine. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/12524152/Effects_of_5_HT1B_receptor_ligands_microinjected_into_the_ventral_tegmental_area_on_cocaine_discrimination_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S001429990202873X DB - PRIME DP - Unbound Medicine ER -