Influence of buprenorphine, butorphanol and nalbuphine on the initiation of intravenous cocaine self-administration in drug naive mice

The influence of different mixed mu-kappa -opioid receptor agonists-antagon ists on cocaine reinforcement was studied using the method of initiation of intravenous cocaine self-administration in naive mice. Self-administration of cocaine was readily initiated according to an inverted U-shaped unit do se-response curve. Buprenorphine, butorphanol and nalbuphine tested against the optimal unit dose of cocaine (0.8 mug per infusion), inhibited initiat ion of cocaine self-administration in a dose-dependent manner. When tested against a scale of cocaine unit doses (0.2 -1.6 mug per infusion) buprenorp hine (0.1 mg/kg, s.c.) and nalbuphine (2 mg/kg, s.c.) produced a shift of t he optimal cocaine dose from 0.8 to 0.4 mug/inf, while butorphanol (1 mg/kg , s.c.) shifted the optimal unit dose of cocaine to the right along the coc aine unit doses axis. Go-administration of naloxone (0.1 mg/kg, s.c.) signi ficantly reduced the effect of buprenorphine but failed to influence the ef fect of nalbuphine and butorphanol on cocaine intake. Taken together, these results suggest that nalbuphine is capable of affecting cocaine's reinforc ing properties in the same manner as buprenorphine during the initiation ph ase of cocaine self-administration behavior, while butorphanol causes the o pposite effect. Although the exact opioid profile of action of the mixed op ioid receptor agonists-antagonists is as yet not precisely known, the prese nt findings suggest that multiple opioid receptor systems (i.e. mu and kapp a) play a role in reinforcing properties of cocaine and that a co-operative interaction between mu- and kappa -opioid systems may be of importance dur ing initiation of cocaine self-administration. (C) 2000 Elsevier Science B. V. All rights reserved.