Effects of 5-HT1B receptor ligands microinjected into the ventral tegmental area on the locomotor and sensitizating effects of cocaine in rats
| Autor: | Edmund Przegaliński, Iwona Papla, Joanna Siwanowicz, Małgorzata Filip |
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| Rok vydání: | 2002 |
| Předmět: |
Agonist
Male Microinjections medicine.drug_class Pyridines Pharmacology Hyperkinesis Motor Activity Serotonin 5-HT1 Receptor Antagonists Drug Administration Schedule Serotonin Agents Cocaine medicine Animals Pharmacology (medical) Drug Interactions Pyrroles Anesthetics Local Rats Wistar Biological Psychiatry Sensitization 5-HT receptor CP-93129 Analysis of Variance Behavior Animal Dose-Response Relationship Drug business.industry Ventral Tegmental Area Antagonist Serotonin 5-HT1 Receptor Agonists Rats Ventral tegmental area Psychiatry and Mental health Dose–response relationship medicine.anatomical_structure Neurology Benzamides Receptor Serotonin 5-HT1B Neurology (clinical) Serotonin business |
| Zdroj: | European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 14(3) |
| ISSN: | 0924-977X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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