Specific Alterations of Extracellular Endocannabinoid Levels in the Nucleus Accumbens by Ethanol, Heroin, and Cocaine Self-AdministrationThe Journal of Neuroscience, April 4, 2007, 27(14):3695-3702;
Ethanol and opiate self-administration are sensitive to manipulations of cannabinoid CB1 receptor function and, from this, a role for the endogenous cannabinoid system in the modulation of drug reward has been hypothesized. However, direct in vivo evidence of drug-induced alterations in brain endocannabinoid (eCB) formation has been lacking.
To address this issue, we explored the effect of drug self-administration on interstitial eCB levels in the nucleus accumbens (NAc) shell using in vivo microdialysis. Ethanol, heroin, and cocaine were compared because the rewarding properties of ethanol and heroin are reduced by CB1 receptor inactivation, whereas cocaine reward is less sensitive to these manipulations.
Together with our previous observation that intra-NAc SR 141716A reduces heroin self-administration, these data provide novel in vivo support for an eCB involvement in the motivational properties of ethanol and heroin but not cocaine.
Furthermore, the selective effects of ethanol and heroin on interstitial 2-AG and AEA provide new insight into the distinct neurochemical profiles produced by these two abused substances.
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