Ethanol-induced extracellular signal regulated kinase: role of dopamine D1 receptors.
BACKGROUND
Addictive drugs activate extracellular signal regulated kinase (ERK) in brain regions critically involved in their affective and motivational properties. The aim of this study was to demonstrate the ethanol-induced activation of ERK in the nucleus accumbens (Acb) and in the extended amygdala [bed nucleus of the stria terminalis lateralis (BSTL) and central nucleus of the amygdala (CeA)] and to highlight the role of dopamine (DA) D(1) receptors in these effects.


METHODS
Ethanol (0.5, 1, and 2 g/kg) was administered by gavage and ERK phosphorylation was determined in the nucleus Acb (shell and core), BSTL, and CeA by immunohistochemistry. The DA D(1) receptor antagonist, SCH 39166 (SCH) (50 microg/kg), was administered 10 minutes before ethanol (1 g/kg).


RESULTS
Quantitative microscopic examination showed that ethanol, dose-dependently increased phospho-ERK immunoreactivity (optical and neuronal densities) in the shell and core of nucleus Acb, BSTL, and CeA. Pretreatment with SCH fully prevented the increases elicited by ethanol (1 g/kg) in all brain regions studied.


CONCLUSIONS
The results of this study indicate that ethanol, similar to other addictive drugs, activates ERK in nucleus Acb and extended amygdala via a DA D(1) receptor-mediated mechanism. Overall, these results suggest that the D(1) receptors/ERK pathway may play a critical role in the motivational properties of ethanol.
Ibba
Federico
F
Department of Toxicology, INN-National Institute of Neuroscience, University of Cagliari, Via Ospedale 72, Cagliari, Italy.
Vinci
Stefania
S
Spiga
Saturnino
S
Peana
Alessandra T
AT
Assaretti
Anna R
AR
Spina
Liliana
L
Longoni
Rosanna
R
Acquas
Elio
E