The Journal of Neuroscience, August 15, 2001, 21(16):6362-6369
Amphetamine-Induced Plasticity of AMPA Receptors in the Ventral
Tegmental Area: Effects on Extracellular Levels of Dopamine and
Glutamate in Freely Moving Rats
Marco
Giorgetti,
Gregory
Hotsenpiller,
Peter
Ward,
Tara
Teppen, and
Marina E.
Wolf
Department of Neuroscience, Finch University of Health
Sciences/The Chicago Medical School, North Chicago, Illinois
60064-3095
Previous electrophysiological studies suggested that the initiation
of behavioral sensitization to cocaine and amphetamine involves a
transient increase in AMPA receptor responsiveness in the ventral
tegmental area (VTA). To test this, we used in vivo
microdialysis to examine the effects of intra-VTA administration of
AMPA (10 µM) and NMDA (100 µM) on dopamine
(DA) and glutamate efflux in the VTA and the nucleus accumbens (NAC),
an important target of VTA DA neurons. We compared rats treated for
5 d with saline or 5 mg/kg amphetamine and withdrawn for 3 or
10-14 d. After 3 d of withdrawal, intra-VTA AMPA increased both
NAC and VTA DA levels to a greater extent in the amphetamine group,
whereas NMDA produced similar effects in the saline and amphetamine
groups. This enhanced responsiveness to AMPA was no longer evident in rats tested 10-14 d after the last injection. In addition, intra-VTA AMPA but not NMDA increased both VTA and NAC glutamate levels in rats
tested 3 d after the last injection of amphetamine but not in
saline controls. After 10-14 d, the responsiveness of glutamate levels
to AMPA was no longer evident in the NAC but persisted in the VTA.
Additional studies indicated that the glutamate effect in the NAC may
involve increased responsiveness of DA receptors within the NAC. These
findings establish an in vivo animal model with which to
explore the consequences of repeated drug administration for AMPA
receptor plasticity in the VTA. They also indicate that repeated
amphetamine leads to potentiated interactions between DA and glutamate transmission.
Key words:
amphetamine; AMPA receptors; behavioral sensitization; microdialysis; nucleus accumbens; plasticity; ventral tegmental
area
Copyright © 2001 Society for Neuroscience 0270-6474/01/21166362-08$05.00/0
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