Inhibition of fatty acid amide hydrolase in the central amygdala alleviates co ‐morbid expression of innate anxiety and excessive alcohol intake

Abstract Fatty acid amide hydrolase (FAAH) is an enzyme that prominently degrades the major endocannabinoid N‐arachidonoylethanolamine (anandamide). Inhibition of this enzyme leads to increased anandamide levels in brain regions that modulate stress and anxiety. Recently, we found that genetically selected Marchigian Sardinian alcohol‐preferring (msP) rats display hyperactive FAAH in amygdalar regions that was associated with increased stress sensitivity and a hyper‐anxious phenotype. Our previous work has also demonstrated that msPs display an innate preference for and excessive consumption of alcohol, potentially reflecting a form of self‐medication to gain relief from hyper‐anxious states. Here, we expand on our previous work by microinjecting the selective FAAH inhibitor URB597 (vehicle, 0.03, 0.1 and 1.0 μg per rat) into the central amygdala (CeA) and basolateral amygdala in msP versus non‐selected Wistar rats to evaluate the effects of localized FAAH inhibition on operant alcohol self‐administration and restraint‐induced anxiety using the elevated plus maze. Intra‐CeA URB597 significantly reduced alcohol self‐administration in msP but not in Wistar rats. Intra‐basolateral amygdala URB597 also attenuated alcohol drinking in msPs, although the effect was less pronounced relative to CeA treatment. In contrast, control experiments administering URB597 into the ventral tegmental area produced no genotypic differences in drinking. We also found that UR...
Source: Addiction Biology - Category: Addiction Authors: Tags: Original Article Source Type: research