title: Rats maintained chronically on buprenorphine show reduced heroin and cocaine seeking in tests of extinction and drug-induced reinstatement.
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.
authors.affiliation: Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montreal, QC, Canada.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sorge
authors.forename: Heshmat
authors.initials: H
authors.lastname: Rajabi
authors.forename: Jane
authors.initials: J
authors.lastname: Stewart
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D001522:Behavior, Animal; D002047:Buprenorphine / Q000008:administration & dosage / Q000009:adverse effects*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003042:Cocaine / Q000008:administration & dosage / Q000009:adverse effects; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004597:Electroshock / Q000379:methods; D005108:Extinction, Psychological / Q000187:drug effects*; D003932:Heroin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000008:administration & dosage / Q000009:adverse effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012054:Reinforcement, Psychology; D012646:Self Administration; D013997:Time Factors
chemical_list: D009294:Narcotics; D002047:Buprenorphine; D003932:Heroin; D003042:Cocaine; D004298:Dopamine