Summary
After the cloning of the dopamine D
1
and D
2
re-
ceptors (13), several additional dopamine recep-
tors were identified. These new subtypes included
the D
3
and D
4
receptors, which are similar to D
2
, and
the D
5
receptor, which is similar to D
1
(46). Al-
though most studies have focused on the role of
dopamine D
1
and D
2
receptors in mediating the ad-
dictive liability of drugs, the lack of selective phar-
macological tools has significantly hampered this
particular field of research. In contrast, recent studies
using selective competitive antagonists have shown
that the dopamine D
3
receptor is involved in drug-
seeking behavior. The present review is intended to
highlight a new, promising area in alcohol research
that focuses on the role of the dopamine D
3
recep-
tor in the addictive properties of ethanol. © 2004 Prous
Science. All rights reserved.
ROLE OF DOPAMINE D
3
RECEPTORS
IN THE ADDICTIVE PROPERTIES OF ETHANOL
Christian A. Heidbreder
1
, Michela Andreoli
1
, Clara Marcon
1
, Panayotis K. Thanos
2
,
Charles R. Ashby, Jr.
3
and Eliot L. Gardner
4
1
Center of Excellence for Drug Discovery in Psychiatry, GlaxoSmithKline Pharmaceuticals, Verona, Italy;
2
Medical Department, Brookhaven National Laboratory, Upton, New York, USA;
3
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions,
Saint Johns University, Jamaica, New York, USA;
4
Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland, USA
Drugs of Today 2004, 40 (4): 355-365
Copyright © 2004 PROUS SCIENCE
CCC: 0025-7656/2004
CONTENTS
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356
Alcoholism: The magnitude of the problem . . . . . . . . . . . . . . . . . . . . . . 356
Effect of alcohol on dopamine function
in the mesolimbic reward system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356
Localization of the dopamine D
3
receptor: Relevance to the mesolimbic
dopamine systems and the rewarding properties of alcohol. . . . . . . . . . 357
Gene polymorphisms at the dopamine D
3
receptor and alcoholism . . . . . . 358
Functional pharmacological studies with dopamine D
3
ligands
and animal models of alcohol-taking and -seeking behaviors. . . . . . . . . 359
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
Correspondence: Christian A. Heidbreder, Department of
Biology, Center of Excellence for Drug Discovery in Psy-
chiatry, GlaxoSmithKline Pharmaceuticals, Via A. Fleming 4,
37135 Verona, Italy. Tel.: +39-045-921-9769; FAX: +39-
045-921-8047. E-mail: Christian_A_Heidbreder@gsk.com