Enhanced acetylcholine release in striatum after chronic amphetamine is NMDA-dependent

BEHAVIORAL. sensitization to chronic amphetamine develops in parallel with an enhancement of amphetamine-stimulated efflux of acetylcholine (ACh) in s triatum. The present study investigated the role of NMDA receptors in the l atter phenomenon. Rats were treated with either saline (1.0 ml/kg, i.p.) or amphetamine (4.0 mg/kg, i.p., b.i.d.) for 12 days followed by a withdrawal period of 2-3 weeks. In vivo microdialysis was employed to measure striata l ACh efflux. Amphetamine challenge (4.0 mg/kg, i.p.) evoked a significant increase in striatal ACh efflux in rats withdrawn from chronic amphetamine while having no significant effect on ACh efflux in saline-pretreated rats. Inclusion of the NMDA receptor antagonist (+/-)-2-amino-5-phoshonopentanoi c acid (APV; 100 mu M) in the perfusion solution blocked the amphetamine-in duced increase in striatal ACh efflux observed in amphetamine-pretreated ra ts. In saline-pretreated animals, the presence of APV had no apparent effec t on the profile of striatal ACh efflux following amphetamine challenge. Th us, the stimulatory effect of amphetamine challenge on striatal ACh efflux that selectively is observed in animals withdrawn from chronic amphetamine is dependent upon NMDA receptor activation. (C) 1999 Lippincott Williams & Wilkins.