Effects of chronic buprenorphine treatment on levels of nucleus accumbens glutamate and on the expression of cocaine-induced behavioral sensitization in rats |
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Authors: | F M Placenza H Rajabi J Stewart |
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Institution: | (1) Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, 7141 Sherbrooke Street West, Montreal, Quebec, H4B 1R6, Canada;(2) Present address: Department of Psychology, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario, M1C 1A4, Canada |
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Abstract: | Rationale 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. Objectives 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. Materials and 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. |
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Keywords: | Buprenorphine Cocaine Sensitization Glutamate Dopamine Nucleus accumbens Microdialysis Locomotor activity |
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