Effects of 5-HT(1B) receptor ligands microinjected into the accumbal shell or core on the sensitization to cocaine in rats.
The present study was designed to find out whether 5-HT(1B) receptors located in subareas of the nucleus accumbens played a role in cocaine sensitization in rats, and whether pharmacological activation of these receptors could modify this drug effect. Male Wistar rats implanted bilaterally with cannulae into the accumbens shell or core were microinjected with GR 55562 (an antagonist of 5-HT(1B) receptors) or CP 93129 (an agonist of 5-HT(1B) receptors). The rats, which were repeatedly (for 5 days) administered with cocaine (10 mg/kg) and then challenged with cocaine (10 mg/kg) after 5-day withdrawal period, showed significantly higher locomotor hyperactivity in comparison with the effect observed in saline-pretreated and cocaine challenged rats. GR 55562 (0.1-10 microg/side), administered for 5 days into the accumbens shell, but not into the core, prior to cocaine dose-dependently attenuated cocaine sensitization. When injected for 5 days into either the accumbens shell or core before cocaine, CP 93129 (0.1-10 microg/side) had no effect on the development of cocaine sensitization. To examine the effects of GR 55562 and CP 93129 on the expression of cocaine sensitization, the drugs were given acutely before a challenge dose of cocaine (10 mg/kg) on day 10. No change in cocaine sensitization was observed after injection of GR 55562 (0.1-10 microg/side) to the either accumbens subregion or after injection of CP 93129 (0.1-10 microg/side) into the core. However, an intra-accumbens shell injection of CP 93129 (10-30 microg/side) increased sensitization to cocaine, and this enhancement was attenuated after local injection of GR 55562 (1 microg/side). Our findings indicate that behavioral sensitization to cocaine may be modulated by 5-HT(1B) receptor ligands in the accumbens shell, but not into the core. They suggest that the inhibition of 5-HT(1B) receptors in the accumbens shell attenuates the development, whereas their pharmacological activation enhances the expression of cocaine sensitization.
Przegaliński
Edmund
E
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343, Kraków, Poland. przegal@if-pan.krakow.pl
Siwanowicz
Joanna
J
Papla
Iwona
I
Filip
Małgorzata
M
D000704:Analysis of Variance; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D001549:Benzamides; D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; 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