Effects of chronic buprenorphine treatment on levels of nucleus accumbens glutamate and on the expression of cocaine-induced behavioral sensitization in rats.
BACKGROUND
Chronic treatment with the mu-opioid receptor agonist, buprenorphine, reduces cocaine-induced behaviors in rats with a history of cocaine self-administration. The mechanisms underlying these actions of buprenorphine remain unclear.


OBJECTIVE
The objective of this study is to investigate the effects of chronic buprenorphine treatment on cocaine-induced activity and levels of glutamate and dopamine (DA) in the nucleus accumbens (NAc) in rats that were preexposed to cocaine or drug-naïve.


METHODS
In experiment 1, basal levels of NAc glutamate were assessed using in vivo microdialysis in cocaine-naïve rats that were treated chronically with buprenorphine (3.0 mg/kg per day) via osmotic minipumps or that underwent sham surgery. In experiment 2, rats were preexposed to seven daily injections of cocaine or saline. After a 12-16-day drug-free period, extracellular levels of NAc glutamate and DA and locomotor activity were assessed simultaneously, before and after an acute injection of cocaine (15 mg/kg, intraperitoneal), in rats under sham and chronic buprenorphine (3.0 mg/kg per day) treatment.


RESULTS
Chronic buprenorphine treatment increased basal levels of glutamate in drug-naïve and cocaine-preexposed rats, blocked the expression of locomotor sensitization to cocaine, and potentiated the NAc DA response to acute cocaine in cocaine-preexposed rats.


CONCLUSIONS
These findings suggest that buprenorphine may block the expression of cocaine sensitization and other cocaine-related behaviors by increasing basal levels of glutamate in the NAc, which would serve to decrease the effectiveness of cocaine or cocaine-associated cues.
Placenza
F M
FM
Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, 7141 Sherbrooke Street West, Montreal, Quebec H4B 1R6, Canada. fplacenza@utsc.utoronto.ca
Rajabi
H
H
Stewart
J
J
D000818:Animals; D001931:Brain Mapping; D002047:Buprenorphine / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans
D018765:Dopamine Uptake Inhibitors; D009292:Narcotic Antagonists; D018698:Glutamic Acid; D002047:Buprenorphine; D003042:Cocaine; D004298:Dopamine