Specific alterations of extracellular endocannabinoid levels in the nucleus accumbens by ethanol, heroin, and cocaine self-administration.
Journal of Neuroscience. 2007-04-04; 27(14): 3695-3702
DOI: 10.1523/jneurosci.4403-06.2007
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1. J Neurosci. 2007 Apr 4;27(14):3695-702.
Specific alterations of extracellular endocannabinoid levels in the nucleus
accumbens by ethanol, heroin, and cocaine self-administration.
Caillé S(1), Alvarez-Jaimes L, Polis I, Stouffer DG, Parsons LH.
Author information:
(1)Laboratoire Neuropsychobiologie des Desadaptations, Université Victor Ségalen
Bordeaux 2, Centre National de la Recherche Scientifique, Unité Mixte de
Recherche 5227, 33076 Bordeaux Cedex, France.
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. Ethanol self-administration significantly increased
dialysate 2-arachidonoylglycerol (2-AG) levels with no concomitant change in
dialysate anandamide (AEA) concentrations. Conversely, heroin self-administration
significantly increased dialysate AEA levels, and induced a subtle but
significant decrease in dialysate 2-AG levels. In each case, the relative change
in dialysate eCB content was significantly correlated with the amount of drug
consumed. In contrast, cocaine self-administration did not alter dialysate levels
of either AEA or 2-AG. Local infusion of the CB1 antagonist SR 141716A into the
NAc significantly reduced ethanol, but not cocaine, self-administration. 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.
DOI: 10.1523/JNEUROSCI.4403-06.2007
PMID: 17409233 [Indexed for MEDLINE]