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The Journal of Neuroscience, April 15, 2002, 22(8):3293-3301
Changes in Extracellular Dopamine Induced by Morphine and
Cocaine: Crucial Control by D2 Receptors
Françoise
Rougé-Pont1, *,
Alessandro
Usiello3, *,
Marianne
Benoit-Marand2, *,
François
Gonon2,
Pier Vincenzo
Piazza1, and
Emiliana
Borrelli3
1 Institut National de la Santé et de la
Recherche Médicale (INSERM) U259, Université Victor
Segalen Bordeaux 2, 33077 Bordeaux Cedex, France, 2 Centre
National de la Recherche Scientifique (CNRS) Unité Mixte de
Recherche 5541, Université V. Segalen Bordeaux 2, 33076 Bordeaux,
France, and 3 Institut de Génétique et de
Biologie Moléculaire et Cellulaire, INSERM, CNRS,
Université Louis Pasteur, 67404 Illkirch Cedex, Communauté
Urbaine de Strasbourg, France
An increase of extracellular dopamine (DA) concentration is a major
neurobiological substrate of the addictive properties of drugs of
abuse. In this article we investigated the contribution of the DA D2
receptor (D2R) in the control of this response. Extracellular DA levels
were measured in the striatum of mice lacking D2R expression (D2R /)
by in vivo microdialysis after administration of the psychostimulant cocaine and the opioid morphine. Interestingly, the
increase in extracellular DA induced by both drugs was strikingly higher in D2R/ than in wild-type littermates. This indicates that
D2Rs play a key role in the modulation of DA release in response to
drugs of abuse. Furthermore, this observation prompted us to investigate the dopaminergic autoreceptor function in the absence of D2
receptor in D2R/ mice. Results obtained using complementary microdialysis and voltammetry analyses show that the autoreceptor function regulating DA release is totally abolished in the absence of
D2R, despite unchanged DA uptake and basal DA efflux. Finally, we
propose that the short isoform D2S receptor of the D2 receptors is the
one controlling change in DA release induced by drugs of abuse. Indeed,
the neurochemical effects of cocaine and morphine are unchanged in
animals with a selective deletion of the long isoform D2L receptor.
Thus, deregulated expression of D2R isoforms might be involved in the
vulnerability of an individual to drug abuse.
Key words:
dopamine; D2 receptors; knock-out mice; dopaminergic
autoreceptors; microdialysis; voltammetry; addictive drugs
*
F.R.P., A.U., and M.B.M. have equally contributed to this work.
Copyright © 2002 Society for Neuroscience 0270-6474/02/2283293-09$05.00/0
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