Acute alcohol exposure in rats (8% ethanol in the liquid diet for a period of 24 h) is associated with a decrease in the levels of endocannabinoids (anandamide and 2-arachidonoyl-glycerol) as well as in various N-acylethanolamines, in different brain regions. In the present study, we wanted to further explore: (i) whether these decreases might be caused by an increase in fatty acid amide hydrolase (FAAH), the enzyme involved in the degradation of N-acylethanolamines including anandamide, and (ii) whether the changes in endocannabinoid levels are accompanied by parallel changes in the major cannabinoid receptor type, the CB(1) receptor, activated by these ligands in the brain. Our data proved that FAAH activity did not increase in any of the four regions analyzed, even it was reduced in the hypothalamus and the prefrontal cortex. Paradoxically, FAAH levels increased in the hypothalamus and, to a lesser extent, in the prefrontal cortex and the amygdala, but not in the caudate-putamen. By contrast, the levels of CB(1) receptors were markedly reduced in the amygdala and prefrontal cortex of these rats, although no changes were seen in the hypothalamus and the caudate-putamen. These results suggest that reductions in the levels of endocannabinoids and related N-acylethanolamines caused by acute alcohol exposure are not originated by an enhanced degradation by FAAH enzyme, but they are associated with low levels of the receptors activated by these ligands, although this parallelism did not occur in all brain regions analyzed. In any case, these observations would support the notion of a general reduction in the activity of the cannabinoid signaling system by acute alcohol exposure.
Effects of a short-term exposure to alcohol in rats on FAAH enzyme and CB1 receptor in different brain areas
2008
Abstract
Acute alcohol exposure in rats (8% ethanol in the liquid diet for a period of 24 h) is associated with a decrease in the levels of endocannabinoids (anandamide and 2-arachidonoyl-glycerol) as well as in various N-acylethanolamines, in different brain regions. In the present study, we wanted to further explore: (i) whether these decreases might be caused by an increase in fatty acid amide hydrolase (FAAH), the enzyme involved in the degradation of N-acylethanolamines including anandamide, and (ii) whether the changes in endocannabinoid levels are accompanied by parallel changes in the major cannabinoid receptor type, the CB(1) receptor, activated by these ligands in the brain. Our data proved that FAAH activity did not increase in any of the four regions analyzed, even it was reduced in the hypothalamus and the prefrontal cortex. Paradoxically, FAAH levels increased in the hypothalamus and, to a lesser extent, in the prefrontal cortex and the amygdala, but not in the caudate-putamen. By contrast, the levels of CB(1) receptors were markedly reduced in the amygdala and prefrontal cortex of these rats, although no changes were seen in the hypothalamus and the caudate-putamen. These results suggest that reductions in the levels of endocannabinoids and related N-acylethanolamines caused by acute alcohol exposure are not originated by an enhanced degradation by FAAH enzyme, but they are associated with low levels of the receptors activated by these ligands, although this parallelism did not occur in all brain regions analyzed. In any case, these observations would support the notion of a general reduction in the activity of the cannabinoid signaling system by acute alcohol exposure.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
