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Role of 5-hydroxytryptamine1B receptors and 5-hydroxytryptamine uptake inhibition in the cocaine-evoked discriminative stimulus effects in rats.
J Physiol Pharmacol. 2001 Jun; 52(2):249-63.JP

Abstract

Mesolimbic dopamine pathways play a critical role in the behavioural effects of cocaine in rodents. Nonetheless, research has also demonstrated involvement of 5-hydroxytryptamine (5-HT; serotonin) transmission in these effects. The present study investigated the ability of selective 5-HT1B receptor ligands and a 5-HT reuptake inhibitor to substitute for or to alter (enhance or antagonise) the discriminative stimulus effects of cocaine. Male Wistar rats were trained to discriminate cocaine (10 mg/kg, i.p.) from saline (i.p.) in a two-choice, water-reinforced fixed ratio (FR) 20 drug discrimination paradigm. In substitution tests, the selective 5-HT1B receptor agonist 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine (CP 94253; 2.5-5 mg/kg, i.p.) and the 5-HT reuptake inhibitor fluoxetine (5-10 mg/kg, i.p.) elicited ca. 40 and 0% drug-lever responding, respectively. In combination experiments, CP 94253 (2.5-5 mg/kg) given with submaximal doses of cocaine (0.3-2.5 mg/kg) produced a leftward shift in the cocaine dose-response curve; pretreatment with CP 94253 (5 mg/kg) prior to a dose of cocaine (2.5 mg/kg) which elicited lower than 40% drug-lever responding, caused full substitution. Fluoxetine (5 and 10 mg/kg) given in combination with a submaximal dose of cocaine (2.5 mg/kg) produced a 100% drug-lever responding. Pretreatment with the 5-HT1B receptor antagonists N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)-1,1'-biphenyl-4 carboxamide (GR 127935; 0.5-5 mg/kg, s.c.) and 3-(3-dimethylamino)-propyl)-4-hydroxy-N-[4-(4-pyridinyl)-phenyl]benzamide (GR 55562; 1 mg/kg, s.c.) failed to modulate the dose-effect curve for cocaine (0.6-5 mg/kg). On the other hand, GR 127935 (5 mg/kg) and GR 55562 (1 mg/kg) significantly attenuated the enhancement of cocaine discrimination evoked by a combination of CP 94253 (5 mg/kg) or fluoxetine (5 mg/kg) and cocaine (2.5 mg/kg). These results indicate that 5-HT1B receptors are not directly involved in the cocaine-induced discriminative stimuli in rats. On the other hand, they indicate that pharmacological stimulation of 5-HT receptors--that also seem to be a target for fluoxetine-mediated increase in 5-HT neurotransmission--can enhance the overall effects of cocaine.

Authors+Show Affiliations

Department of Pharmacology, Polish Academy of Science, Krakow.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11453104

Citation

Filip, M, et al. "Role of 5-hydroxytryptamine1B Receptors and 5-hydroxytryptamine Uptake Inhibition in the Cocaine-evoked Discriminative Stimulus Effects in Rats." Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, vol. 52, no. 2, 2001, pp. 249-63.
Filip M, Nowak E, Papla I, et al. Role of 5-hydroxytryptamine1B receptors and 5-hydroxytryptamine uptake inhibition in the cocaine-evoked discriminative stimulus effects in rats. J Physiol Pharmacol. 2001;52(2):249-63.
Filip, M., Nowak, E., Papla, I., & Przegaliński, E. (2001). Role of 5-hydroxytryptamine1B receptors and 5-hydroxytryptamine uptake inhibition in the cocaine-evoked discriminative stimulus effects in rats. Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, 52(2), 249-63.
Filip M, et al. Role of 5-hydroxytryptamine1B Receptors and 5-hydroxytryptamine Uptake Inhibition in the Cocaine-evoked Discriminative Stimulus Effects in Rats. J Physiol Pharmacol. 2001;52(2):249-63. PubMed PMID: 11453104.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of 5-hydroxytryptamine1B receptors and 5-hydroxytryptamine uptake inhibition in the cocaine-evoked discriminative stimulus effects in rats. AU - Filip,M, AU - Nowak,E, AU - Papla,I, AU - Przegaliński,E, PY - 2001/7/17/pubmed PY - 2002/1/5/medline PY - 2001/7/17/entrez SP - 249 EP - 63 JF - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JO - J. Physiol. Pharmacol. VL - 52 IS - 2 N2 - Mesolimbic dopamine pathways play a critical role in the behavioural effects of cocaine in rodents. Nonetheless, research has also demonstrated involvement of 5-hydroxytryptamine (5-HT; serotonin) transmission in these effects. The present study investigated the ability of selective 5-HT1B receptor ligands and a 5-HT reuptake inhibitor to substitute for or to alter (enhance or antagonise) the discriminative stimulus effects of cocaine. Male Wistar rats were trained to discriminate cocaine (10 mg/kg, i.p.) from saline (i.p.) in a two-choice, water-reinforced fixed ratio (FR) 20 drug discrimination paradigm. In substitution tests, the selective 5-HT1B receptor agonist 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine (CP 94253; 2.5-5 mg/kg, i.p.) and the 5-HT reuptake inhibitor fluoxetine (5-10 mg/kg, i.p.) elicited ca. 40 and 0% drug-lever responding, respectively. In combination experiments, CP 94253 (2.5-5 mg/kg) given with submaximal doses of cocaine (0.3-2.5 mg/kg) produced a leftward shift in the cocaine dose-response curve; pretreatment with CP 94253 (5 mg/kg) prior to a dose of cocaine (2.5 mg/kg) which elicited lower than 40% drug-lever responding, caused full substitution. Fluoxetine (5 and 10 mg/kg) given in combination with a submaximal dose of cocaine (2.5 mg/kg) produced a 100% drug-lever responding. Pretreatment with the 5-HT1B receptor antagonists N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)-1,1'-biphenyl-4 carboxamide (GR 127935; 0.5-5 mg/kg, s.c.) and 3-(3-dimethylamino)-propyl)-4-hydroxy-N-[4-(4-pyridinyl)-phenyl]benzamide (GR 55562; 1 mg/kg, s.c.) failed to modulate the dose-effect curve for cocaine (0.6-5 mg/kg). On the other hand, GR 127935 (5 mg/kg) and GR 55562 (1 mg/kg) significantly attenuated the enhancement of cocaine discrimination evoked by a combination of CP 94253 (5 mg/kg) or fluoxetine (5 mg/kg) and cocaine (2.5 mg/kg). These results indicate that 5-HT1B receptors are not directly involved in the cocaine-induced discriminative stimuli in rats. On the other hand, they indicate that pharmacological stimulation of 5-HT receptors--that also seem to be a target for fluoxetine-mediated increase in 5-HT neurotransmission--can enhance the overall effects of cocaine. SN - 0867-5910 UR - https://www.unboundmedicine.com/medline/citation/11453104/Role_of_5_hydroxytryptamine1B_receptors_and_5_hydroxytryptamine_uptake_inhibition_in_the_cocaine_evoked_discriminative_stimulus_effects_in_rats_ L2 - http://www.jpp.krakow.pl/journal/archive/06_01/pdf/249_06_01_article.pdf DB - PRIME DP - Unbound Medicine ER -