Buprenorphine alters ethanol self-administration in rats: dose-response and time-dependent effects.
Buprenorphine is a partial opioid agonist derived from thebaine and has high affinity for mu and kappa opioid receptors. The present study investigated dose-response (0.03, 0.15, 0.3, 3 mg/kg) and time-dependent effects of buprenorphine (1.5 or 4 h post-treatment) on EtOH self-administration in outbred Sprague-Dawley rats. Freely feeding and drinking rats were trained to initiate EtOH self-administration for 1 h daily using the ascending concentration procedure, wherein they were provided with increasing concentrations of EtOH at 2, 5, 7, 9 and 11% (v/v), respectively. Water was concurrently available with each concentration. Animals were maintained on a given concentration of EtOH for 5 days. By day 21, animals began their stabilization on the 11% regimen and remained on this concentration throughout the remainder of the study. EtOH and water consumption were recorded daily at both 10- and 60-min intervals. At 1.5 h post-buprenorphine, all test doses greatly suppressed both EtOH and water intake at the 10-min interval. At the 60-min interval, all but the lowest dose (0.03 mg/kg) significantly suppressed EtOH intake, while only the highest dose (3 mg/kg) suppressed water intake. In contrast to the suppressant profile observed at 1.5 h post-buprenorphine, at 4 h post-buprenorphine the lower doses (0.03 and 0.15 mg/kg) significantly increased EtOH intake while the higher doses (0.3 and 3 mg/kg) continued to suppress intake. None of the doses of buprenorphine altered water intake 4 h post-buprenorphine. The results support previous research demonstrating the utility of low doses of buprenorphine in suppressing behavior rewarded by a non-opioid drug.
June
H L
HL
Department of Psychology, Purdue School of Science, Indiana University-Purdue University, Indianapolis 46202, USA.
Cason
C R
CR
Chen
S H
SH
Lewis
M J
MJ
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013997:Time Factors
D000701:Analgesics, Opioid; D000431:Ethanol; D002047:Buprenorphine