title: Acetaldehyde elicits ERK phosphorylation in the rat nucleus accumbens and extended amygdala.
abstract: 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 D(1) 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 D(1) receptors stimulation in acetaldehyde-elicited ERK phosphorylation, we studied the effect of the D(1) receptor antagonist, SCH 39166. Pretreatment with the D(1) receptor antagonist (50 μg/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.
authors.affiliation: Department of Toxicology, University of Cagliari, 09124 Cagliari, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Vinci
authors.forename: Federico
authors.initials: F
authors.lastname: Ibba
authors.forename: Rosanna
authors.initials: R
authors.lastname: Longoni
authors.forename: Liliana
authors.initials: L
authors.lastname: Spina
authors.forename: Saturnino
authors.initials: S
authors.lastname: Spiga
authors.forename: Elio
authors.initials: E
authors.lastname: Acquas
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism / Q000494:pharmacology*; D020268:Alcohol-Induced Disorders, Nervous System / Q000201:enzymology / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects* / Q000201:enzymology; D000818:Animals; D002492:Central Nervous System Depressants / Q000378:metabolism / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D048049:Extracellular Signal-Regulated MAP Kinases; D000079:Acetaldehyde