¹Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montreal, QC, Canada

Correspondence: Dr J Stewart, Center for Studies in Behavioral Neurobiology, Concordia University, SP-A-244, 7141 Sherbrooke St. W., Montreal, QC, Canada H4B 1R6. Tel: +1 514 848 2424 ext.2193; Fax: +1 514 848 2817; E-mail: jane.stewart@concordia.ca

Received 15 October 2004; Revised 25 January 2005; Accepted 27 January 2005; Published online 30 March 2005.

Abstract

Buprenorphine is being introduced as a maintenance therapy in opioid addiction, but it is not clear how buprenorphine will affect co-use of cocaine in opioid users. We examined the effects of chronic buprenorphine (BUP0: 0.0 mg/kg/day; BUP1.5: 1.5 mg/kg/day; BUP3: 3.0 mg/kg/day) on the locomotor activity effects of acute heroin (0.25 mg/kg, subcutaneously (s.c.)) and cocaine (20 mg/kg, intraperitoneally (i.p.)). Buprenorphine had no effect on the stimulatory effect of heroin, but potentiated the locomotor response to cocaine. To investigate further the interactions between buprenorphine (BUP1.5 and BUP3), heroin (0.125, 0.25 and 0.375 mg/kg, s.c.), and cocaine (10, 20 and 30 mg/kg, i.p.), we used in vivo microdialysis and high-performance liquid chromatography to analyze extracellular levels of dopamine (DA) in the nucleus accumbens (NAc). Buprenorphine attenuated the heroin-induced rise in NAc DA, but greatly potentiated the cocaine-induced rise. Finally, we examined the potential of the highest dose of buprenorphine (BUP3) to reduce heroin and cocaine seeking in the presence of drug-associated cues under extinction conditions and in tests for reinstatement induced by heroin (0.25 mg/kg, s.c.), cocaine (20 mg/kg, i.p.), and 15-min footshock stress (0.8 mA, 0.5 s/shock, 40 s mean OFF time) in rats trained to self-administer both drugs. Buprenorphine reduced heroin and cocaine seeking during extinction and following acute heroin and cocaine priming injections, but had no effect on stress-induced reinstatement. These results indicate that the suppression of responding following priming injections of drugs did not result from reduced motor activity, but possibly from a reduction in the salience of drug-associated cues induced by chronic buprenorphine treatment.