Adolescent Stimulation of D2 Receptors Alters the Maturation of Dopamine-dependent Goal-Directed Behavior
Neuropsychopharmacol. 2013-02-26; 38(8): 1566-1574
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1. Neuropsychopharmacology. 2013 Jul;38(8):1566-74. doi: 10.1038/npp.2013.55. Epub
2013 Feb 26.
Adolescent stimulation of D2 receptors alters the maturation of
dopamine-dependent goal-directed behavior.
Naneix F(1), Marchand AR, Pichon A, Pape JR, Coutureau E.
(1)CNRS, Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, UMR
5287, Talence, France.
Adolescence is a period of high sensitivity to drugs and rewards, characterized
by the immaturity of decision-making abilities. A chronic stimulation of reward
systems during this period might constitute a factor of vulnerability to the
development of psychiatric disorders. However, the long-term consequences of such
an exposure have seldom been explored. Here, we investigate at the adult age the
effects of chronic dopamine (DA) stimulation during adolescence on both the
maturation of DA systems and the cognitive processes underlying goal-directed
actions. We first demonstrate that chronic stimulation of D2 receptors by
quinpirole during adolescence alters the development of DA systems. This
treatment has particularly prominent effects on the mesocortical DA pathway where
it decreases DA fibers density, DA concentration, and DA receptors expression.
Furthermore, we show that quinpirole-treated rats exhibit specific impairments in
instrumental goal-directed behavior, as they fail to adapt their action when
action-outcome relationships change in a contingency degradation procedure. These
results therefore highlight the vulnerability of DA system and prefrontal areas
to prolonged stimulation during adolescence, and its potential long-term impact
on cognitive functions.
PMID: 23443719 [Indexed for MEDLINE]