Influence of NOS inhibitors on changes in ACH release and NO level in the brain elicited by amphetamine neurotoxicity

We studied the possible role of neurotoxicity in the d,l-amphetamine (AMPH)-induced release of acetylcholine (ACH) in the nucleus accumbens (Nac) and the involvement of endogenous NO in this process. For determination of ACH release the Nac was superfused using the push-pull-technique. NO was directly measured using the electron paramagnetic resonance technique. Repeated administration of AMPH increased ACH release by about 400%. N-nitro-L-arginine (L-NNA) and 7-nitroindazole (7-NI) nearly abolished the AMPH-induced increase in ACH release. AMPH increased NO as web as lipid peroxidation (LPO) products in the cortex. L-NNA and 7-NI substantially diminished NO increase. AMPH-evoked LPO was only slightly reduced by these compounds. It is concluded that AMPH enhances ACH release through increased NO synthesis and induces neurotoxicity via NO and by LPO independent NO generation. (C) 1999 Lippincott Williams & Wilkins.