TY - JOUR
T1 - Amphetamine-induced glutamate efflux in the rat ventral tegmental area is prevented by MK-801, SCH 23390, and ibotenic acid lesions of the prefrontal cortex
AU - Wolf, Marina E.
AU - Xue, Chang Jiang
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - We showed previously that amphetamine challenge produces a delayed increase in glutamate efflux in the ventral tegmental area of both naive and chronic amphetamine-treated rats. The present study examined the mechanisms underlying this response. The NMDA receptor antagonist MK-801 (0.1 mg/kg, i.p.) or the D1 dopamine receptor antagonist SCH 23390 (0.1 mg/kg, i.p.), given 30 min before acute amphetamine (5 mg/kg, i.p.), prevented amphetamine- induced glutamate efflux. Neither antagonist by itself altered glutamate efflux. Ibotenic acid lesions of the prefrontal cortex similarly prevented amphetamine-induced glutamate efflux, while producing a trend toward decreased basal glutamate levels (82.8% of sham group). Previous work has shown that the doses of NMDA and D1 receptor antagonists used in this study prevent the induction of behavioral sensitization when coadministered repeatedly with amphetamine, and that identical prefrontal cortex lesions performed before repeated amphetamine prevent the induction of ambulatory sensitization. Thus, treatments that prevent acute amphetamine from elevating glutamate efflux in the ventral tegmental area also prevent repeated amphetamine from eliciting behavioral sensitization. These findings suggest that repeated elevation of glutamate levels during a chronic amphetamine regimen may contribute to the cascade of neuroadaptations within the ventral tegmental area that enables the induction of sensitization.
AB - We showed previously that amphetamine challenge produces a delayed increase in glutamate efflux in the ventral tegmental area of both naive and chronic amphetamine-treated rats. The present study examined the mechanisms underlying this response. The NMDA receptor antagonist MK-801 (0.1 mg/kg, i.p.) or the D1 dopamine receptor antagonist SCH 23390 (0.1 mg/kg, i.p.), given 30 min before acute amphetamine (5 mg/kg, i.p.), prevented amphetamine- induced glutamate efflux. Neither antagonist by itself altered glutamate efflux. Ibotenic acid lesions of the prefrontal cortex similarly prevented amphetamine-induced glutamate efflux, while producing a trend toward decreased basal glutamate levels (82.8% of sham group). Previous work has shown that the doses of NMDA and D1 receptor antagonists used in this study prevent the induction of behavioral sensitization when coadministered repeatedly with amphetamine, and that identical prefrontal cortex lesions performed before repeated amphetamine prevent the induction of ambulatory sensitization. Thus, treatments that prevent acute amphetamine from elevating glutamate efflux in the ventral tegmental area also prevent repeated amphetamine from eliciting behavioral sensitization. These findings suggest that repeated elevation of glutamate levels during a chronic amphetamine regimen may contribute to the cascade of neuroadaptations within the ventral tegmental area that enables the induction of sensitization.
KW - Amphetamine
KW - Behavioral sensitization
KW - D1 dopamine receptors
KW - NMDA receptors-Prefrontal cortex
KW - Ventral tegmental area
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U2 - 10.1046/j.1471-4159.1999.0731529.x
DO - 10.1046/j.1471-4159.1999.0731529.x
M3 - Article
C2 - 10501198
AN - SCOPUS:0032842206
VL - 73
SP - 1529
EP - 1538
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 4
ER -