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, Marina Wolf

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

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 We compared rats treated for 5 d with saline or 5 mg/kg amphetamine and withdrawn for 3 or 10-14 d. After 3 d of withdrawal, intra-VTA AMPA increased both NAC and VTA DA levels to a greater extent in the amphetamine group, whereas NMDA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.

Original languageEnglish (US)
Pages (from-to)6362-6369
Number of pages8
JournalJournal of Neuroscience
Volume21
Issue number16
StatePublished - Aug 15 2001
Externally publishedYes

Fingerprint

Ventral Tegmental Area
AMPA Receptors
Amphetamine
Glutamic Acid
Dopamine
Nucleus Accumbens
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
N-Methylaspartate
Tegmentum Mesencephali
Injections
Dopaminergic Neurons
Microdialysis
Dopamine Receptors
Cocaine
Animal Models

Keywords

  • AMPA receptors
  • Amphetamine
  • Behavioral sensitization
  • Microdialysis
  • Nucleus accumbens
  • Plasticity
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Amphetamine-induced plasticity of AMPA receptors in the ventral tegmental area : Effects on extracellular levels of dopamine and glutamate in freely moving rats. / Giorgetti, Marco; Hotsenpiller, Gregory; Ward, Peter; Teppen, Tara; Wolf, Marina.

In: Journal of Neuroscience, Vol. 21, No. 16, 15.08.2001, p. 6362-6369.

Research output: Contribution to journalArticle

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