Buprenorphine reduces alcohol drinking through activation of the nociceptin/orphanin FQ-NOP receptor system.
BACKGROUND
Activation of the NOP receptor by its endogenous ligand nociceptin/orphanin FQ reduces ethanol intake in genetically selected alcohol preferring Marchigian Sardinian alcohol preferring (msP) rats. Here we evaluated whether buprenorphine, a partial agonist at micro-opioid and NOP receptors, would reduce ethanol consumption in msP rats via activation of NOP receptors.


METHODS
Marchigian Sardinian alcohol preferring rats trained to drink 10% alcohol 2 hours/day were injected with buprenorphine (.03, .3, 3.0, or 6.0 mg/kg intraperitoneally [IP]) 90 min before access to ethanol.


RESULTS
Similar to prototypical micro-agonists, the two lowest doses of buprenorphine significantly increased ethanol consumption (p < .01); in contrast, the two highest doses reduced it (p < .05). Pretreatment with naltrexone (.25 mg/kg IP) prevented the increase of ethanol intake induced by .03 mg/kg of buprenorphine (p < .001) but did not affect the inhibition of ethanol drinking induced by 3.0 mg/kg of buprenorphine. Conversely, pretreatment with the selective NOP receptor antagonist UFP-101 (10.0 or 20.0 microg/rat) abolished the suppression of ethanol drinking by 3.0 mg/kg of buprenorphine.


CONCLUSIONS
Buprenorphine has dualistic effects on ethanol drinking; low doses increase alcohol intake via stimulation of classic opioid receptors, whereas higher doses reduce it via activation of NOP receptors. We suggest that NOP agonistic properties of buprenorphine might be useful in the treatment of alcoholism.
Department of Experimental Medicine and Public Health, University of Camerino, Camerino, Italy. roberto.ciccocioppo@unicam.it
Roberto
R
Ciccocioppo
Daina
D
Economidou
Roberto
R
Rimondini
Wolfgang
W
Sommer
Maurizio
M
Massi
Markus
M
Heilig
D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002047:Buprenorphine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects; D004333:Drug Administration Routes; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D009271:Naltrexone / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D018847:Opioid Peptides / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000502:physiology; D013997:Time Factors; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D002047:Buprenorphine; D000431:Ethanol; D009271:Naltrexone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); C000722285:Oprl1 protein, rat