The effects of chronic buprenorphine on intake of heroin and cocaine in rats and its effects on nucleus accumbens dopamine levels during self-administration.
BACKGROUND
Buprenorphine reduces both heroin and cocaine intake in opioid addicts, but the mechanisms remain unclear.


OBJECTIVE
To determine the effects of chronic buprenorphine treatment on intake of heroin and/or cocaine and measure nucleus accumbens (NAc) dopamine (DA) levels during self-administration.


METHODS
In experiment 1, plasma levels of buprenorphine were determined in rats with buprenorphine osmotic minipumps (3.0 mg/kg/day) using an ELISA. In experiment 2, rats self-administered (FR1) one dose of heroin [(0.025, 0.05, or 0.1 mg/kg/infusion (inf)] and one dose of cocaine (0.25, 0.5, or 1.0 mg/kg/inf) before and under sham or chronic buprenorphine treatment (1.5 or 3.0 mg/kg/day). In experiment 3, the effect of sham or chronic buprenorphine treatment (3.0) on heroin (0.05 mg/kg/inf) or cocaine (0.5 mg/kg/inf) self-administration under FR5 and progressive ratio (PR) schedules was evaluated. In experiment 4, in vivo microdialysis sampling from the NAc was carried out during heroin (0.05 mg/kg/inf) or cocaine (0.5 mg/kg/inf) self-administration (FR1) under sham or buprenorphine treatment (3.0).


RESULTS
Buprenorphine levels in plasma were stable over time. Buprenorphine treatment had no effect on total heroin intake at any dose or under any schedule, whereas it suppressed cocaine intake at all doses and under all schedules. Buprenorphine enhanced basal levels of DA, attenuated the NAc DA response to heroin, and enhanced the DA response to cocaine. It is interesting to note that buprenorphine increased the latency to respond to drug-associated cues at the start of self-administration sessions.


CONCLUSIONS
Chronic buprenorphine reduces cocaine, but not heroin, intake and possibly reduces drug seeking by reducing the salience of the drug-associated cues.
Sorge
Robert E
RE
Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, SP 244, Montreal, Quebec, H4B 1R6, Canada.
Stewart
Jane
J
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002047:Buprenorphine / Q000097:blood / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D003932:Heroin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009292:Narcotic Antagonists / Q000097:blood / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration; D013997:Time Factors
D000697:Central Nervous System Stimulants; D009292:Narcotic Antagonists; D009294:Narcotics; D002047:Buprenorphine; D003932:Heroin; D003042:Cocaine; D004298:Dopamine