Effects of 5-HT1B receptor ligands microinjected into the ventral tegmental area on the locomotor and sensitizating effects of cocaine in rats.
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.
Przegaliński
Edmund
E
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland. przegal@if-pan.krakow.pl
Papla
Iwona
I
Siwanowicz
Joanna
J
Filip
Małgorzata
M
D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal; D001549:Benzamides / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D018490:Serotonin Agents / Q000494:pharmacology*; D017557:Ventral Tegmental Area / Q000187:drug effects*
D000779:Anesthetics, Local; D001549:Benzamides; D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D018490:Serotonin Agents; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; C103477:3-(3-(dimethylamino)propyl)-4-hydroxy-N-(4-(4-pyridinyl)phenyl)benzamide; D003042:Cocaine