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Effects of 5-HT1B receptor ligands microinjected into the ventral tegmental area on the locomotor and sensitizating effects of cocaine in rats.
Eur Neuropsychopharmacol. 2004 May; 14(3):217-25.EN

Abstract

The present study was aimed at finding out whether 5-HT(1B) receptors located in the ventral tegmental area (VTA) played a role in the locomotor hyperactivity induced by a single dose of cocaine and in the sensitization evoked by repeated exposure to the psychostimulant in rats. Male Wistar rats, implanted bilaterally with cannulae in the VTA, were microinjected with GR 55562 (an antagonist of 5-HT(1B) receptors) or CP 93129 (an agonist of 5-HT(1B) receptors). GR 55562 (0.3-3 microg/side) did not affect locomotor hyperactivity response to a single dose of cocaine (10 mg/kg). CP 93129 in a dose of 1 microg/side (but not lower), which stimulated basal locomotor activity, enhanced the cocaine-induced locomotor hyperactivity. The rats that were treated repeatedly (for 5 days) with cocaine (10 mg/kg) and then challenged with cocaine (10 mg/kg) after 5-day withdrawal period (day 10 of the experiment) showed significantly higher locomotor hyperactivity compared to the effect observed in saline-pretreated and cocaine-challenged rats. GR 55562 (a dose of 3 microg/side, but not lower), administered for 5 days into the VTA just prior to daily cocaine, attenuated cocaine sensitization. When injected for 5 days into the VTA, CP 93129 (0.03-0.1 microg/side) enhanced the development of cocaine sensitization. The enhancing effect of CP 93129 (0.1 microg/side) was blocked by GR 55562 (1 microg/side). To examine the effects of GR 55562 and CP 93129 on the expression of cocaine sensitization, the 5-HT(1B) receptor ligands were given acutely before the challenge dose of cocaine administered on day 10. No change in cocaine sensitization was observed after intra-VTA microinjections of GR 55562 (0.3-3 microg/side) or CP 93129 (0.1-1 microg/side). Our findings suggest that 5-HT(1B) receptors located in the VTA play a permissive role in the development of cocaine sensitization, but are not involved in the locomotor hyperactivity induced by a single dose of cocaine or in the expression of the sensitization to the psychostimulant.

Authors+Show Affiliations

Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland. przegal@if-pan.krakow.plNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15056481

Citation

Przegaliński, Edmund, et al. "Effects of 5-HT1B Receptor Ligands Microinjected Into the Ventral Tegmental Area On the Locomotor and Sensitizating Effects of Cocaine in Rats." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 14, no. 3, 2004, pp. 217-25.
Przegaliński E, Papla I, Siwanowicz J, et al. Effects of 5-HT1B receptor ligands microinjected into the ventral tegmental area on the locomotor and sensitizating effects of cocaine in rats. Eur Neuropsychopharmacol. 2004;14(3):217-25.
Przegaliński, E., Papla, I., Siwanowicz, J., & Filip, M. (2004). Effects of 5-HT1B receptor ligands microinjected into the ventral tegmental area on the locomotor and sensitizating effects of cocaine in rats. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 14(3), 217-25.
Przegaliński E, et al. Effects of 5-HT1B Receptor Ligands Microinjected Into the Ventral Tegmental Area On the Locomotor and Sensitizating Effects of Cocaine in Rats. Eur Neuropsychopharmacol. 2004;14(3):217-25. PubMed PMID: 15056481.
* 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 the locomotor and sensitizating effects of cocaine in rats. AU - Przegaliński,Edmund, AU - Papla,Iwona, AU - Siwanowicz,Joanna, AU - Filip,Małgorzata, PY - 2002/09/13/received PY - 2003/02/20/revised PY - 2003/06/17/accepted PY - 2004/4/2/pubmed PY - 2004/6/24/medline PY - 2004/4/2/entrez SP - 217 EP - 25 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 14 IS - 3 N2 - The present study was aimed at finding out whether 5-HT(1B) receptors located in the ventral tegmental area (VTA) played a role in the locomotor hyperactivity induced by a single dose of cocaine and in the sensitization evoked by repeated exposure to the psychostimulant in rats. Male Wistar rats, implanted bilaterally with cannulae in the VTA, were microinjected with GR 55562 (an antagonist of 5-HT(1B) receptors) or CP 93129 (an agonist of 5-HT(1B) receptors). GR 55562 (0.3-3 microg/side) did not affect locomotor hyperactivity response to a single dose of cocaine (10 mg/kg). CP 93129 in a dose of 1 microg/side (but not lower), which stimulated basal locomotor activity, enhanced the cocaine-induced locomotor hyperactivity. The rats that were treated repeatedly (for 5 days) with cocaine (10 mg/kg) and then challenged with cocaine (10 mg/kg) after 5-day withdrawal period (day 10 of the experiment) showed significantly higher locomotor hyperactivity compared to the effect observed in saline-pretreated and cocaine-challenged rats. GR 55562 (a dose of 3 microg/side, but not lower), administered for 5 days into the VTA just prior to daily cocaine, attenuated cocaine sensitization. When injected for 5 days into the VTA, CP 93129 (0.03-0.1 microg/side) enhanced the development of cocaine sensitization. The enhancing effect of CP 93129 (0.1 microg/side) was blocked by GR 55562 (1 microg/side). To examine the effects of GR 55562 and CP 93129 on the expression of cocaine sensitization, the 5-HT(1B) receptor ligands were given acutely before the challenge dose of cocaine administered on day 10. No change in cocaine sensitization was observed after intra-VTA microinjections of GR 55562 (0.3-3 microg/side) or CP 93129 (0.1-1 microg/side). Our findings suggest that 5-HT(1B) receptors located in the VTA play a permissive role in the development of cocaine sensitization, but are not involved in the locomotor hyperactivity induced by a single dose of cocaine or in the expression of the sensitization to the psychostimulant. SN - 0924-977X UR - https://www.unboundmedicine.com/medline/citation/15056481/Effects_of_5_HT1B_receptor_ligands_microinjected_into_the_ventral_tegmental_area_on_the_locomotor_and_sensitizating_effects_of_cocaine_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924977X03001068 DB - PRIME DP - Unbound Medicine ER -