Effects of single and dual administration of cocaine and ethanol on opioid and ORL1 receptor expression in rat CNS: an autoradiographic study.
The co-abuse of cocaine and ethanol is common among human addicts and has been reported to produce a stronger increase of euphoria as compared to either drug given alone. Both cocaine and ethanol increase the extracellular dopamine concentration in the nucleus accumbens, a terminal region in the mesolimbic dopamine pathway. In addition, both cocaine and ethanol affect the endogenous opioid system, which in turn alters the activity of the mesolimbic dopamine pathway. We have carried out quantitative autoradiography mapping of the opioid receptors as well as the opioid receptor-like 1 receptor in the brains of rats treated with both single and dual cocaine and ethanol. Rats received acute cocaine, ethanol or both drugs in combination. Ethanol alone or in combination with cocaine modulated the receptor densities in rat central nervous system. The kappa receptor densities were generally decreased, while both the mu and the opioid receptor-like 1 receptors were up-regulated. The mu opioid receptor levels were mainly increased in non-cortical regions, whereas the opioid receptor-like 1 receptors were increased in cortical structures. No changes in delta opioid receptors were observed. Cocaine alone did not influence the receptor levels in any of the treatment groups.
Rosin
Asa
A
Department of Clinical Neuroscience, Experimental Drug Addiction Research Section, Karolinska Institutet, CMM L8: 01, S-171 76, Stockholm, Sweden.
Kitchen
Ian
I
Georgieva
Jeanette
J
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001665:Binding Sites; D001931:Brain Mapping; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D004095:Dihydropyridines / Q000493:pharmacokinetics; D004338:Drug Combinations; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000493:pharmacokinetics; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009842:Oligopeptides / Q000493:pharmacokinetics; D018847:Opioid Peptides / Q000187:drug effects / Q000378:metabolism*; D010091:Oximes / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium / Q000493:pharmacokinetics; D000094942:Nociceptin Receptor
D000779:Anesthetics, Local; D002492:Central Nervous System Depressants; D003042:Cocaine; D004095:Dihydropyridines; D004338:Drug Combinations; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D000431:Ethanol; D009842:Oligopeptides; D018847:Opioid Peptides; D010091:Oximes; D011957:Receptors, Opioid; D014316:Tritium; D000094942:Nociceptin Receptor; C059567:deltorphin; C060208:deltorphin I, Ala(2)-; C084978:milameline; C000722285:Oprl1 protein, rat