Effects of 7-nitroindazole, an NOS inhibitor on methamphetamine-induced dopaminergic and serotonergic neurotoxicity in mice

被引:58
作者
Ali, SF
Itzhak, Y
机构
[1] US FDA, Div Neurotoxicol, Neurochem Lab, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA
[2] Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL 33101 USA
来源
NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES | 1998年 / 844卷
关键词
D O I
10.1111/j.1749-6632.1998.tb08227.x
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
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 [H-3]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 injection of METH caused a significant decrease in the concentration of serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA). Treatment with 7-NI partially blocked the depletion of 5-HT and completely blocked the reduction in 5-HIAA levels, The administration of 7-NI/saline (group ii) affected neither the tissue concentration of DA, 5-HT and their metabolites (DOPAC, HVA and 5-HIAA) nor the binding parameters of [H-3]-mazindol compared to control (vehicle/saline) values, 7-NI had no significant effect on the animals' body temperature, and it did not affect METH-induced hyperthermia, These findings indicate a role for nitric oxide in METH-induced neurotoxicity and also suggest that blockage of NOS may be beneficial for the management of Parkinson's disease.
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页码:122 / 130
页数:9
相关论文
共 35 条
[1]   Methamphetamine-induced dopaminergic toxicity in mice - Role of environmental temperature and pharmacological agents [J].
Ali, SF ;
Newport, GD ;
Slikker, W .
CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES, 1996, 801 :187-198
[2]   LOW ENVIRONMENTAL TEMPERATURES OR PHARMACOLOGICAL AGENTS THAT PRODUCE HYPOTHERMIA DECREASE METHAMPHETAMINE NEUROTOXICITY IN MICE [J].
ALI, SF ;
NEWPORT, GD ;
HOLSON, RR ;
SLIKKER, W ;
BOWYER, JF .
BRAIN RESEARCH, 1994, 658 (1-2) :33-38
[3]  
BECKMAN JS, 1990, P NATL ACAD SCI USA, V87, P1621
[4]   EFFECTS OF A COLD ENVIRONMENT OR AGE ON METHAMPHETAMINE-INDUCED DOPAMINE RELEASE IN THE CAUDATE PUTAMEN OF FEMALE RATS [J].
BOWYER, JF ;
GOUGH, B ;
SLIKKER, W ;
LIPE, GW ;
NEWPORT, GD ;
HOLSON, RR .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1993, 44 (01) :87-98
[5]  
BOWYER JF, 1994, J PHARMACOL EXP THER, V268, P1571
[6]  
BOWYER JF, 1992, J PHARMACOL EXP THER, V260, P817
[7]  
DiMonte DA, 1996, J NEUROCHEM, V67, P2443
[8]   LONG-TERM CHANGES IN DOPAMINERGIC INNERVATION OF CAUDATE-NUCLEUS AFTER CONTINUOUS AMPHETAMINE ADMINISTRATION [J].
ELLISON, G ;
EISON, MS ;
HUBERMAN, HS ;
DANIEL, F .
SCIENCE, 1978, 201 (4352) :276-278
[9]   EFFECT OF ACUTE AND CHRONIC METHAMPHETAMINE TREATMENT ON TYROSINE HYDROXYLASE ACTIVITY IN BRAIN AND ADRENAL MEDULLA [J].
FIBIGER, HC ;
MCGEER, EG .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1971, 16 (02) :176-&
[10]   LONG-LASTING DEPLETION OF STRIATAL DOPAMINE BY A SINGLE INJECTION OF AMPHETAMINE IN IPRINDOLE-TREATED RATS [J].
FULLER, RW ;
HEMRICKLUECKE, S .
SCIENCE, 1980, 209 (4453) :305-307