Effect of D-amphetamine on the extracellular concentrations of glutamate and dopamine in iprindole-treated rats.
A single administration of D-amphetamine and iprindole has been reported to produce selective, long-lasting decreases in brain dopamine (DA) content because of axon terminal degeneration. It has been found that the noncompetitive glutamate (GLU) antagonist, MK 801, blocks D-amphetamine-induced DA depletion in iprindole-treated rats. In the present study, the effect of D-amphetamine (9.2 mg/kg) and iprindole (10 mg/kg) on the extracellular concentrations of DA and GLU was determined in the striatum of awake, freely moving rats by the use of in vivo microdialysis. D-Amphetamine significantly increased DA and GLU efflux in the striatum of iprindole-treated rats as compared to the vehicle-treated group. The increase in the extracellular concentration of GLU occurred 4-6 hr following drug administration. The concentration of DA was decreased significantly in the striatum of D-amphetamine and iprindole-treated rats 7 days following administration as compared to the vehicle-treated group. Inhibition of tyrosine hydroxylase after alpha-methylparatyrosine (150 mg/kg) administration attenuated D-amphetamine-induced DA and GLU release. The DA antagonist, haloperidol (1 mg/kg), blocked D-amphetamine-induced GLU release without affecting the increase in the extracellular concentration of DA produced by the combination of D-amphetamine and iprindole. Both alpha-methylparatyrosine and haloperidol blocked the depletion of DA in the striatum 7 days after D-amphetamine and iprindole as compared to the vehicle group. In addition, administration of MK-801 (2 mg/kg) 2 hr after D-amphetamine significantly attenuated the long-term (7 day) decrease in striatal DA content produced by the combination of D-amphetamine and iprindole.2+
Nash
J F
JF
Department of Psychiatry, Case Western Reserve University, Cleveland, OH 44106-5000.
Yamamoto
B K
BK
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006220:Haloperidol / Q000494:pharmacology; D007488:Iprindole / Q000494:pharmacology*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D005971:Glutamates; D008781:Methyltyrosines; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D019805:alpha-Methyltyrosine; D007488:Iprindole; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D003913:Dextroamphetamine; D004298:Dopamine