Phasic dopamine release evoked by abused substances requires cannabinoid receptor activation.
Transient surges of dopamine in the nucleus accumbens are associated with drug seeking. Using a voltammetric sensor with high temporal and spatial resolution, we demonstrate differences in the temporal profile of dopamine concentration transients caused by acute doses of nicotine, ethanol, and cocaine in the nucleus accumbens shell of freely moving rats. Despite differential release dynamics, all drug effects are uniformly inhibited by administration of rimonabant, a cannabinoid receptor (CB1) antagonist, suggesting that an increase in endocannabinoid tone facilitates the effects of commonly abused drugs on subsecond dopamine release. These time-resolved chemical measurements provide unique insight into the neurobiological effectiveness of rimonabant in treating addictive disorders.
Cheer
Joseph F
JF
Department of Chemistry and Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA.
Wassum
Kate M
KM
Sombers
Leslie A
LA
Heien
Michael L A V
ML
Ariansen
Jennifer L
JL
Aragona
Brandon J
BJ
Phillips
Paul E M
PE
Wightman
R Mark
RM
D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D013287:Illicit Drugs / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077285:Rimonabant; D013997:Time Factors
D063385:Cannabinoid Receptor Modulators; D013287:Illicit Drugs; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant; D004298:Dopamine