COMPARATIVE EFFECTS OF SELECTIVE KAPPA-OPIOID RECEPTOR AGONISTS ON DOPAMINE LEVELS IN THE DORSAL CAUDATE OF FREELY MOVING RATS

Microdialysis was utilized to evaluate the effects of selective K-opioid receptor agonists on dopamine levels in the dorsal caudate of conscious rats. Subcutaneous administration of equivalent antinociceptive doses of spiradoline - (+/-)-(5 alpha,7 alpha,8 beta)-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]benzeneacetamide - (U62066; 12 mg/kg), BRL 52656 - (2S)-1- [(4-trifluoromethylphenyl)acetyl]-2-[(1-pyrrolidinyl)methyl]piperidine - (2 mg/kg) and enadoline - (-)-(5 beta,7 beta,8 alpha)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]benzo[b]furan-4-acetamide - (CI-977; 0.1 mg/kg) produced similar, statistically significant decreases in dorsal caudate dopamine levels; BRL 53001 - (2S)-2-(dimethylaminomethyl)-1-[(5,6,7,8-tetrahydro-5-oxo-2-naphthyl)acetyl]piperidine - (12 mg/kg) was, however, without effect. At a higher dose (36 mg/kg), BRL 53001 also caused a significant reduction in dopamine levels. BRL 52974 - 4-(1-pyrrolidinylmethyl)5-[(3,4-dichlorophenyl)acetyl]-4,5,6,7-t-etrahydroimidazo[4,5-c]pyridine, a selective kappa-opioid receptor agonist with limited ability to cross the blood brain barrier or produce antinociceptive effects, had no effect on dopamine levels at 10 mg/kg s.c. Overall, these findings suggest that selective K-opioid receptor agonists decrease dopamine levels in the dorsal caudate of rats via a central locus of action. Furthermore, compared to other K-opioid receptor agonists, BRL 53001 appears to have a reduced propensity to decrease dopamine levels at equianalgesic doses.