Buprenorphine Reduces Alcohol Drinking

Study Author(s):

Ciccocioppo, Roberto Economidou, Daina Rimondini, Roberto Sommer, Wolfgang Massi, Maurizio Heilig, Markus

Journal Name:

Biological Psychiatry, 2007, Vol.61(1), pp.4-12

Publication Date:

2007

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 μ-opioid and NOP receptors, would reduce ethanol consumption in msP rats via activation of NOP receptors. 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. Similar to prototypical μ-agonists, the two lowest doses of buprenorphine significantly increased ethanol consumption ( < .01); in contrast, the two highest doses reduced it ( < .05). Pretreatment with naltrexone (.25 mg/kg IP) prevented theincrease of ethanol intake induced by .03 mg/kg of buprenorphine ( < .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 μg/rat) abolished thesuppression of ethanol drinking by 3.0 mg/kg of buprenorphine. 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.