Behavioral and neurochemical interactions between cocaine and buprenorphine: implications for the pharmacotherapy of cocaine abuse.
Intravenous self-administration studies in nonhuman primates suggest that the opioid receptor agonist-antagonist buprenorphine may be useful in the pharmacotherapy of cocaine abuse. In the present studies, behavioral and neurochemical interactions between cocaine and buprenorphine were examined using a conditioned place preference (CPP) procedure and in vivo microdialysis. Cocaine-induced CPP was linearly related to the dose administered (0-5.0 mg/kg). Buprenorphine (0-0.9 mg/kg) also elicited CPP in a dose-related manner; an inverted U-shaped function was obtained. Subthreshold doses of cocaine (1.5 mg/kg) and buprenorphine (0.01 mg/kg), themselves incapable of eliciting CPP, produced a significant CPP when given together. Moderate doses of cocaine (5.0 mg/kg) and buprenorphine (0.075 mg/kg), which were individually capable of eliciting CPP, produced a significantly larger CPP when given in combination. In the in vivo microdialysis studies, a low dose of buprenorphine (0.01 mg/kg) produced a progressive increase in extracellular dopamine in the nucleus accumbens, reaching approximately 200% of basal levels after 5 hr. Cocaine (5.0 mg/kg) rapidly increased extracellular dopamine concentrations (180% of basal values within 20 min), which returned to baseline in 2 to 3 hr. This effect of cocaine was significantly potentiated by coadministering buprenorphine (0.01 mg/kg); under this condition the peak increase in extracellular dopamine reached 260% of baseline values. These neurochemical findings are consistent with the CPP results and indicate that buprenorphine can interact with cocaine in a synergistic manner. In contrast to previous speculations, these results suggest that buprenorphine may enhance rather than attenuate the rewarding properties of cocaine.