Recent advances suggest that acetaldehyde mediates some of the neurobiological properties of ethanol. In a recent study, we have shown that ethanol elicits the phosphorylation of extracellular signal-regulated kinase (pERK) in the nucleus accumbens and extended amygdala, via a dopamine D1 receptor-mediated mechanism.
The aim of this study was to determine whether acetaldehyde and ethanol-derived acetaldehyde elicit the activation of ERK in the nucleus accumbens and extended amygdala.
The effects of acetaldehyde (10 and 20 mg/kg) and ethanol (1 g/kg), administered to rats intragastrically, were assessed by pERK peroxidase immunohistochemistry. To establish the role of ethanol-derived acetaldehyde, the alcohol dehydrogenase inhibitor, 4-methylpyrazole (90 mg/kg), and the acetaldehyde-sequestering agent, D-penicillamine (50 mg/kg), were administered before ethanol.
Acetaldehyde increased pERK immunoreactivity in the nucleus accumbens and extended amygdala. Inhibition of ethanol metabolism and sequestration of newly synthesized acetaldehyde completely prevented ERK activation by ethanol. In addition, to establish the role of D1 receptors stimulation in acetaldehyde-elicited ERK phosphorylation, we studied the effect of the D1 receptor antagonist, SCH 39166.
Pretreatment with the D1 receptor antagonist (50
g/kg) fully prevented acetaldehyde-elicited ERK activation.Overall, these results indicate that ethanol activates ERK by means of its metabolic conversion into acetaldehyde and strengthen the view that acetaldehyde is a centrally acting compound with a pharmacological profile similar to ethanol.
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