title: Influence of NOS inhibitors on changes in ACH release and NO level in the brain elicited by amphetamine neurotoxicity.
abstract: 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 well 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.
authors.affiliation: Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow.
authors.forename: V
authors.initials: V
authors.lastname: Bashkatova
authors.forename: M
authors.initials: M
authors.lastname: Kraus
authors.forename: H
authors.initials: H
authors.lastname: Prast
authors.forename: A
authors.initials: A
authors.lastname: Vanin
authors.forename: K
authors.initials: K
authors.lastname: Rayevsky
authors.forename: A
authors.initials: A
authors.lastname: Philippu
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000662:Amphetamines / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000662:Amphetamines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine