Intermittent ethanol consumption depresses endocannabinoid-signaling in the dorsolateral striatum of rat

Addiction Biology Unit, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenburg, Box 410, 405 30 Gothenburg, Sweden.
Neuropharmacology (Impact Factor: 5.11). 12/2011; 61(7):1160-5. DOI: 10.1016/j.neuropharm.2011.01.014
Source: PubMed


Recent research suggests that adaptations elicited by drugs of abuse share common features with traditional learning models, and that drugs of abuse cause long-term changes in behavior by altering synaptic function and plasticity. In this study, endocannabinoid (eCB) signaling in the dorsolateral striatum, a brain region vital for habit formation, was evaluated in acutely isolated brain slices from ethanol (EtOH)-consuming rats and control rats. EtOH-consuming rats had free access to a 20% EtOH solution for three 24 hour sessions a week during seven weeks and consumed an average of 3.4 g/kg per session. eCB-mediated long-lasting disinhibition (DLL) of population spike (PS) amplitude induced by moderate frequency stimulation was impaired in EtOH-consuming rats, and was not restored by the muscarinic receptor antagonist scopolamine (10 μM). The lack of DLL could be linked to a reduced GABA(A) receptor tone, since bicuculline-mediated disinhibition of striatal output was significantly reduced in slices from EtOH-consuming rats. However, eCB signaling induced by high frequency stimulation (HFS) was also impaired in slices from EtOH-consuming rats and isolated control rats. Activation of presynaptic cannabinoid 1 receptors (CB1R) with WIN55,212-2 (250 nM, 1 μM) significantly modulated PS amplitude in slices from age-matched control rats while slices from EtOH-consuming rats remained unaffected, indicating that eCB signaling is inhibited at a level that is downstream from CB1R activation. Intermittent alcohol intake for seven weeks might thus be sufficient to modulate a presynaptic mechanism that needs to be synergized with CB1R activation for induction of long-term depression (LTD). In conclusion, alcohol consumption inhibits striatal eCB signaling in a way that could be of importance for understanding the neurological underpinnings of addictive behavior.

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    • "Cnr1 acts within the endocannabinoid (eCB) system, involved in modulating neurophysiological processes controlling mood, memory, pain sensation, and appetite [10]. Cnr1 is also thought to be involved in the neuropharmacological effects of alcohol [11] through inhibition of glutaminergic and GABAergic interneurons [12]. Variations in this gene or alterations in its expression are also associated with mood disorders, particularly fear and anxiety phenotypes [13]. "
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    • "Acute exposure of striatal slices to moderate ethanol doses substantially reduces eCB-mediated DLL in the dorsolateral striatum (Clarke et al., 2010). DLL is also significantly reduced in the dorsolateral striatum of rats following longterm voluntary alcohol consumption (Adermark et al., 2011). Endocannabinoid-mediated LTD at inhibitory striatal synapses is also reduced by acute ethanol, though no significant ethanol effects are evident on LTD of excitatory synapses (Clarke et al., 2010). "
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