Acute and repeated systemic amphetamine administration: effects on extracellular glutamate, aspartate, and serine levels in rat ventral tegmental area and nucleus accumbens

J Neurochem. 1996 Jul;67(1):352-63. doi: 10.1046/j.1471-4159.1996.67010352.x.


Recent work indicates an important role for excitatory amino acids in behavioral sensitization to amphetamine. We therefore examined, using in vivo microdialysis in awake rats, the effects of amphetamine on efflux of glutamate, aspartate, and serine in the ventral tegmental area and nucleus accumbens, brain regions important for the initiation and expression of amphetamine sensitization, respectively. Water-pretreated and amphetamine-pretreated rats were compared to determine if sensitization altered such effects. In both brain regions, Ca2+-dependent efflux of glutamate accounted for approximately 20% of basal glutamate efflux. A challenge injection of water or 2.5 mg/kg of amphetamine did not significantly alter glutamate, aspartate, or serine efflux in the ventral tegmental area or nucleus accumbens of water- or amphetamine-pretreated rats. However, 5 mg/kg of amphetamine produced a gradual increase in glutamate efflux in both regions that did not reverse, was observed in both water- and amphetamine-pretreated rats, and was prevented by haloperidol. Although increased glutamate efflux occurred with too great a delay to mediate acute behavioral responses to amphetamine, it is possible that repeated augmentation of glutamate efflux during repeated amphetamine administration results in compensatory changes in levels of excitatory amino acid receptors in the ventral tegmental area and nucleus accumbens that contribute to development of expression of amphetamine sensitization.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / drug effects
  • Amino Acids / metabolism*
  • Amphetamine / pharmacology*
  • Animals
  • Aspartic Acid / drug effects
  • Aspartic Acid / metabolism
  • Calcium / pharmacology
  • Central Nervous System Stimulants / pharmacology*
  • Dose-Response Relationship, Drug
  • Extracellular Space / metabolism
  • Glutamic Acid / drug effects
  • Glutamic Acid / metabolism
  • Male
  • Microdialysis
  • Neurons / cytology
  • Neurons / drug effects
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sensitivity and Specificity
  • Serine / drug effects
  • Serine / metabolism
  • Time Factors
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / drug effects*
  • Ventral Tegmental Area / metabolism


  • Amino Acids
  • Central Nervous System Stimulants
  • Aspartic Acid
  • Glutamic Acid
  • Serine
  • Amphetamine
  • Calcium