TY - JOUR
T1 - Acute and repeated systemic amphetamine administration
T2 - Effects on extracellular glutamate, aspartate, and serine levels in rat ventral tegmental area and nucleus accumbens
AU - Xue, Chang Jiang
AU - Ng, Jeffrey P.
AU - Li, Yong
AU - Wolf, Marina E.
PY - 1996/7
Y1 - 1996/7
N2 - 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 ~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 or expression of amphetamine sensitization.
AB - 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 ~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 or expression of amphetamine sensitization.
KW - Amphetamine
KW - Glutamate
KW - Microdialysis
KW - Nucleus accumbens
KW - Sensitization
KW - Ventral tegmental area
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U2 - 10.1046/j.1471-4159.1996.67010352.x
DO - 10.1046/j.1471-4159.1996.67010352.x
M3 - Article
C2 - 8667013
AN - SCOPUS:0029931274
SN - 0022-3042
VL - 67
SP - 352
EP - 363
JO - Journal of neurochemistry
JF - Journal of neurochemistry
IS - 1
ER -