INVESTIGADORES
RUBINSTEIN Marcelo
artículos
Título:
Role of dopamine D1-like receptors in methamphetamine locomotor responses of D2 receptor knockout mice
Autor/es:
M. A. KELLY; M. J. LOW; M. RUBINSTEIN; T. J. PHILLIPS
Revista:
GENES BRAIN AND BEHAVIOR
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Año: 2008 vol. 7 p. 568 - 577
ISSN:
1601-1848
Resumen:
Behavioral sensitization to psychostimulants manifests
as an increased locomotor response with repeated administration.
Dopamine systems are accepted to play
a fundamental role in sensitization, but the role of
specific dopamine receptor subtypes has not been completely
defined. This study used the combination of
dopamine D2 receptor-deficient mice and a D1-like antagonist
to examine dopamine D1 and D2 receptor involvement
in acute and sensitized locomotor responses to
methamphetamine. Absence of the dopamine D2 receptor
resulted in attenuation of the acute stimulant effects
of methamphetamine. Mutant and wild-type mice exhibited
sensitization that lasted longer within the time
period of the challenge test in the mutant animals.
Pretreatment with the D1-like receptor antagonist SCH
23390 produced more potent reductions in the acute and
sensitized locomotor responses to methamphetamine in
D2 receptor-deficient mice than in wild-type mice; however,
the expression of locomotor sensitization when
challenged with methamphetamine alone was equivalently
attenuated by previous treatment with SCH 23390.
These data suggest that dopamine D2 receptors play
a key role in the acute stimulant and sensitizing effects of
methamphetamine and act in concert with D1-like receptors
to influence the acquisition of methamphetamine-
induced behavioral sensitization, traits that may
influence continued methamphetamine use.