Effects of 7-Nitroindazole, an NOS Inhibitor on Methamphetamine-Induced Dopaminergic and Serotonergic Neurotoxicity in Mice(a)

Annals of the New York Academy of Sciences
Syed F Ali, Y Itzhak

Abstract

Methamphetamine (METH) is one of the major drugs of abuse that is postulated to cause neurotoxicity by depleting dopamine (DA) and its metabolites, high-affinity DA uptake sites, and the activity of tyrosine hydroxylase. The present study was undertaken to investigate whether the relatively selective, neuronal nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI), protects against METH-induced neurotoxicity. Male Swiss Webster mice received the following injections intraperitoneally (i.p.) 3 times (every 3 hr): (i) vehicle/saline, (ii) 7-NI (25 mg/kg)/saline, (iii) vehicle/METH (5 mg/kg), and (iv) 7-NI (25 mg/kg)/METH (5 mg/kg). On the second day, groups (i) and (iii) received two vehicle injections and groups (ii) and (iv) received two 7-NI injections (25 mg/kg each). The administration of vehicle/METH resulted in 68, 44 and 55% decreases in the concentration of DA, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA), respectively, and a 48% decrease in the number of [(3)H]mazindol binding sites in the striatum compared to control values. The treatment with 7-NI (group iv) provided a full protection against the depletion of DA and its metabolites, and the loss of dopamine transporter binding sites. Multiple...Continue Reading

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Citations

Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Madhavan P N NairJessica L Reynolds
Jul 11, 2003·Annals of the New York Academy of Sciences·Ashraf VirmaniSyed Ali
Apr 15, 2004·Psychopharmacology·M Isabel ColadoA Richard Green
Jul 19, 2003·Pharmacological Reviews·A Richard GreenM Isabel Colado
Feb 19, 2005·The Journal of Pharmacology and Experimental Therapeutics·David M Thomas, Donald M Kuhn
Oct 1, 2004·The Journal of Pharmacology and Experimental Therapeutics·Altaf S DarveshGary A Gudelsky
Jun 18, 2020·Life·Carla FerreiraAlexandre Quintas
Dec 12, 2012·The Journal of Pharmacology and Experimental Therapeutics·Danielle M FriendAshley N Fricks-Gleason
Mar 6, 2016·The International Journal of Neuropsychopharmacology·Liliana MendietaRosario Moratalla
Nov 21, 2000·Annals of the New York Academy of Sciences·D M Kuhn, T J Geddes
Aug 7, 2013·Neurotoxicity Research·Danielle M FriendKristen A Keefe
Nov 16, 2004·Annals of the New York Academy of Sciences·Ashraf VirmaniSyed F Ali
Nov 18, 2015·Oxidative Medicine and Cellular Longevity·Vessela VitchevaMitka Mitcheva
Jun 23, 1999·Drug Discovery Today·M P SmithA P Kozikowski
Aug 16, 2005·Brain Research·Altaf S Darvesh, Gary A Gudelsky
Mar 31, 2009·Brain Research Reviews·Irina N Krasnova, Jean Lud Cadet

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