Effects of serotonin (5-HT)(1B) receptor ligands, microinjected into accumbens subregions, on cocaine discrimination in rats.
Recent data indicate a significant input of serotonin (5-HT) on mesoaccumbens dopamine-dependent behavioral effects of cocaine in rats. The present study investigated the role of 5-HT(1B) receptors in nucleus accumbens subregions (the shell and the core) and the effect of stimulation of those receptors in the discriminative stimulus effects of cocaine in rats. 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 20 procedure. After reaching the cocaine-saline discrimination criterion, rats were stereotaxically implanted with bilateral cannulae in the accumbens shell or core, and then were microinjected with selective 5-HT(1B) receptor ligands. In substitution studies, microinjections of the 5-HT(1B) receptor antagonist GR 55562 (0.1-10 microg/side) or the 5-HT(1B) receptor agonist CP 93129 (0.1-10 microg/side) into accumbens subregions did not evoke cocaine-lever responding. Pretreatment with the 5-HT(1B) receptor antagonist GR 55562 (0.1-10 microg/side) in the accumbens shell or core failed to modulate the discriminative stimulus effects of cocaine (5 mg/kg). Combination tests using a fixed dose of CP 93129 (1-10 microg/side) into the accumbens shell prior to cocaine administration (0.6-5.0 mg/kg) did not affect cocaine discrimination. CP 93129 (1 microg/side, but not 0.1 microg/side) microinjected in the accumbens core, and low doses of systemic cocaine (0.6-2.5 mg/kg) produced a leftward shift in the cocaine dose-response curve and a decrease in its ED(50) value. GR 55562 (1 microg/side) significantly attenuated the enhancement of cocaine discrimination evoked by a combination of CP 93129 (1 microg/side) and cocaine (1.25 mg/kg or 2.5 mg/kg). These results seem to exclude a major role for the accumbens shell and core 5-HT(1B) receptors in controlling the discriminative stimulus effects of cocaine. However, they do suggest that the stimulation of 5-HT(1B) receptors in the accumbens core, but not in the shell, enhances cocaine discrimination in rats.
Filip
Małgorzata
M
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31343 Kraków, Poland.
Papla
Iwona
I
Nowak
Ewa
E
Jungersmith
Kelly
K
Przegaliński
Edmund
E
D000818:Animals; D001522:Behavior, Animal; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology
D001549:Benzamides; D008024:Ligands; 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