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Role of dopamine D1 receptors and extracellular signal regulated kinase in the motivational properties of acetaldehyde as assessed by place preference conditioning

Spina, Liliana and Longoni, Rosanna and Vinci, Stefania and Ibba, Federico and Peana, Alessandra Tiziana and Muggironi, Giulia and Spiga, Saturnino and Acquas, Elio (2010) Role of dopamine D1 receptors and extracellular signal regulated kinase in the motivational properties of acetaldehyde as assessed by place preference conditioning. Alcoholism: Clinical and Experimental Research, Vol. 34 (4), p. 607-616. eISSN 1530-0277. Article.

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DOI: 10.1111/j.1530-0277.2009.01129.x

Abstract

Background: The role of dopamine D1 receptors and Extracellular signal Regulated Kinase (ERK) in the motivational properties of drugs can be studied by place-conditioning. Recent advances have shown that the motivational properties of ethanol, determined by place-conditioning, are mediated by its metabolic conversion into acetaldehyde. To date, the role of D1 receptors and ERK activation in acetaldehyde-elicited place preference has not been determined. The aim of this study was to assess the role of D1 receptors blockade and MEK inhibition in the acquisition of acetaldehyde-elicited conditioned place preference.
Methods: Male Sprague–Dawley rats were subjected to repeated pairings with 1 compartment of the conditioning apparatus immediately following acetaldehyde (20 mg ⁄ kg i.g.) or ethanol (1 g ⁄ kg i.g.) administration. The D1 receptor antagonist, SCH 39166 (50 μg ⁄ kg s.c.), was administered 10 minutes before acetaldehyde or ethanol administration. In order to study the role of activated ERK in the acetaldehyde-elicited place preference, rats were administered the MEK inhibitor, PD98059 (1, 30, and 90 μg i.c.v.), 10 or 30 minutes before acetaldehyde. To verify the specificity of these effects, we also studied whether PD98059 pretreatment could affect morphine (1 mg/kg s.c.)-elicited place preference.
Results: Both acetaldehyde and ethanol elicited significant place preferences and these were prevented by pretreatment with SCH 39166. In addition, pretreatment with PD98059, dose- (30 and 90 but not 1 μg i.c.v.) and time- (10 but not 30 minutes before) dependently, prevented the acquisition of acetaldehyde- and significantly reduced the acquisition of morphine-elicited conditioned place preference.
Conclusions: These results confirm that acetaldehyde and ethanol elicit conditioned place preference and demonstrate that D1 receptors are critically involved in these effects. Furthermore, the finding that PD98059 prevents the acquisition of acetaldehyde-elicited conditioned place preference highlights the importance of the D1 receptors–ERK pathway in its motivational effects.

Item Type:Article
ID Code:5938
Status:Published
Refereed:Yes
Uncontrolled Keywords:Acetaldehyde, conditioned place preference, extracellular signal regulated, kinases, ethanol, morphine, PD98059, SCH 39166
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze del farmaco
Publisher:Blackwell / Wiley
eISSN:1530-0277
Copyright Holders:© 2010 by the Research Society on Alcoholism
Deposited On:14 Apr 2011 10:36

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