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 kappa-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)ace tyl] piperidine--(12 mg/kg) was, however, without effect. At a higher dose (36 mg/kgP, BRL 53001 also caused a significant reduction in dopamine levels. BRL 52974--4-(1-pyrrolidinylmethyl) 5-[(3,4-dichlorophenyl)acetyl]-4,5,6,7-tetrahydroimidazo[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 kappa-opioid receptor agonists decrease dopamine levels in the dorsal caudate of rats via a central locus of action. Furthermore, compared to other kappa-opioid receptor agonists, BRL 53001 appears to have a reduced propensity to decrease dopamine levels at equianalgesic doses.
Department of Biology, Smith Kline Beecham Farmaceutici, Milan, Italy.
P
P
Zaratin
G D
GD
Clarke
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008297:Male; D017551:Microdialysis; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013329:Structure-Activity Relationship
D000700:Analgesics; D000889:Anti-Arrhythmia Agents; D001572:Benzofurans; D004232:Diuretics; D011725:Pyridines; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C088382:BRL 52974; C067110:enadoline; C051272:spiradoline; D004298:Dopamine