Acute and repeated systemic amphetamine administration: effects on extracellular glutamate, aspartate, and serine levels in rat ventral tegmental area and nucleus accumbens.
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.
Xue
C J
CJ
Department of Neuroscience, Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois 60064-3095, USA.
Ng
J P
JP
Li
Y
Y
Wolf
M E
ME
D000596:Amino Acids / Q000187:drug effects / Q000378:metabolism*; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D012694:Serine / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000596:Amino Acids; D000697:Central Nervous System Stimulants; D001224:Aspartic Acid; D018698:Glutamic Acid; D012694:Serine; D000661:Amphetamine; D002118:Calcium