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 Previous Article
Journal of Neuroscience, Vol 16, 2411-2420, Copyright © 1996 by Society for Neuroscience
D1 dopamine receptor activation is necessary for the induction of sensitization by amphetamine in the ventral tegmental area
P Vezina
Department of Psychiatry, The University of Chicago, Illinois 60637, USA.
Repeated intermittent exposure to amphetamine produces long-term
enhancements in the ability of this drug to produce locomotion and increase
extracellular dopamine (DA) in the nucleus accumbens (NAcc). Three
experiments were conducted to evaluate the role played by D1 DA receptors
in the production of these changes in response to amphetamine. Rats were
preexposed to amphetamine, alone or with a DA receptor antagonist, and
tested for sensitization 1-3 weeks after the last drug injection. On the
test for sensitization, locomotor (experiments 1 and 2) and NAcc DA
(experiment 3) responses of the animals to a systemic amphetamine injection
were assessed. In the first experiment, systemic injections of the D1 DA
receptor antagonist SCH23390, but not other DA receptor antagonists with
greater affinity for D2 DA and 5-HT2 receptors, blocked the development of
locomotor sensitization produced by systemic injections of amphetamine. In
the second experiment, locomotor sensitization induced by infusion of
amphetamine into the ventral tegmental area (VTA) was blocked when these
injections were preceded by systemic injections of SCH23390. Finally, in
experiment three, co-injecting SCH23390, but not its inactive enantiomer,
with amphetamine into the VTA during preexposure prevented sensitization of
the NAcc DA response to this drug. These results indicate that while D2 DA
receptor activation is not necessary for the induction of locomotor
sensitization to amphetamine, D1 DA receptors located in the VTA play a
critical role in the development of sensitized locomotor and NAcc DA
response to this drug.
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