Ethanol-Induced Extracellular Signal Regulated Kinase: Role of Dopamine D1 Receptors

Authors

  • Federico Ibba,

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    • *

      FI and SV contributed equally to this work.

  • Stefania Vinci,

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    • *

      FI and SV contributed equally to this work.

  • Saturnino Spiga,

    1. From the Departments of Toxicology (FI, SV, LS, RL, EA) and Animal Biology and Ecology (SS), INN—National Institute of Neuroscience (LS, RL, EA), University of Cagliari, Cagliari, Italy; and Department of Drug Sciences (ATP, ARA), University of Sassari, Sassari, Italy; Centre of Excellence for the Study of Neurobiology of Addictions (EA), Cagliari, Italy.
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  • Alessandra T. Peana,

    1. From the Departments of Toxicology (FI, SV, LS, RL, EA) and Animal Biology and Ecology (SS), INN—National Institute of Neuroscience (LS, RL, EA), University of Cagliari, Cagliari, Italy; and Department of Drug Sciences (ATP, ARA), University of Sassari, Sassari, Italy; Centre of Excellence for the Study of Neurobiology of Addictions (EA), Cagliari, Italy.
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  • Anna R. Assaretti,

    1. From the Departments of Toxicology (FI, SV, LS, RL, EA) and Animal Biology and Ecology (SS), INN—National Institute of Neuroscience (LS, RL, EA), University of Cagliari, Cagliari, Italy; and Department of Drug Sciences (ATP, ARA), University of Sassari, Sassari, Italy; Centre of Excellence for the Study of Neurobiology of Addictions (EA), Cagliari, Italy.
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  • Liliana Spina,

    1. From the Departments of Toxicology (FI, SV, LS, RL, EA) and Animal Biology and Ecology (SS), INN—National Institute of Neuroscience (LS, RL, EA), University of Cagliari, Cagliari, Italy; and Department of Drug Sciences (ATP, ARA), University of Sassari, Sassari, Italy; Centre of Excellence for the Study of Neurobiology of Addictions (EA), Cagliari, Italy.
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  • Rosanna Longoni,

    1. From the Departments of Toxicology (FI, SV, LS, RL, EA) and Animal Biology and Ecology (SS), INN—National Institute of Neuroscience (LS, RL, EA), University of Cagliari, Cagliari, Italy; and Department of Drug Sciences (ATP, ARA), University of Sassari, Sassari, Italy; Centre of Excellence for the Study of Neurobiology of Addictions (EA), Cagliari, Italy.
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  • Elio Acquas

    1. From the Departments of Toxicology (FI, SV, LS, RL, EA) and Animal Biology and Ecology (SS), INN—National Institute of Neuroscience (LS, RL, EA), University of Cagliari, Cagliari, Italy; and Department of Drug Sciences (ATP, ARA), University of Sassari, Sassari, Italy; Centre of Excellence for the Study of Neurobiology of Addictions (EA), Cagliari, Italy.
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Reprint requests: Elio Acquas, PhD, Department of Toxicology, Via Ospedale, 72, I-09124 Cagliari, Italy; Fax: +39-070-6758623; E-mail: acquas@unica.it

Abstract

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) D1 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 D1 receptor antagonist, SCH 39166 (SCH) (50 μg/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 D1 receptor-mediated mechanism. Overall, these results suggest that the D1 receptors/ERK pathway may play a critical role in the motivational properties of ethanol.

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