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  • 1
    ISSN: 1435-1463
    Keywords: Nitric oxide (NO·) ; methamphetamine ; neurotoxicity ; dopamine ; serotonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We examined effects of nitric oxide (NO·) synthesis inhibition on methamphetamine (MA)-induced dopaminergic and serotonergic neurotoxicity. The toxic dose of MA (5 mg/kg, sc, X4) significantly decreased contents of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum (ST), and significantly decreased contents of serotonin (5-HT) in the ST, nucleus accumbens (NA) and medial frontal contex (MFC). Coadministration with a NO· synthase inhibitor, Nω-nitro-L-arginine methyl ester (LNAME) (30 mg/kg, ip, X2), reduced the MA-induced decreases in contents of DA, DOPAC and HVA in the ST, but not reduced the MA-induced decreases in contents of 5-HT in the ST, NA and MFC. These findings suggest that the MA-induced dopaminergic, but not serotonergic neurotoxicity, may be related to the neural process such as NO· formation caused by the activation of postsynaptic DA receptor.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1463
    Keywords: Neuroleptics ; dopamine ; prolactin ; hypothalamus ; clozapine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two atypical neuroleptic agents, clozapine and fluperlapine, produced rapid elevations in plasma PRL concentrations that were similar in magnitude to those produced by haloperidol. However, the PRL response to clozapine or fluperlapine was of much shorter duration than that elicited by haloperidol. Clozapine, but neither fluperlapine nor haloperidol, produced a rapid increase in the activity of tuberoinfundibular dopamine (TIDA) neurons, as evidenced by an enhanced accumulation of dihydroxyphenylalanine (DOPA) in the median eminence after the inhibition of DOPA decarboxylase. The clozapine-induced increase in DOPA accumulation was evident within 30 minutes after its administration and persisted for at least 4 hours. The clozapine-induced increase in the activity of TIDA neurons may account, in part, for the abbreviated PRL response to this neuroleptic. In addition, ability to produce a short-lived increase in PRL secretion in the rat appears to be common to the atypicl neuroleptic drugs.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1463
    Keywords: Methamphetamine ; neurotoxicity ; N-methyl-D-aspartate ; dopamine ; serotonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Protective effects of NMDA antagonists on dopaminergic and serotonergic neurotoxicity produced by methamphetamine (MA) were examined. Four injections of MA (7.5 mg/kg, s.c., at 2 h intervals) caused significant decrements (40–60% of control values) in levels of dopamine (DA) and its metabolites in the rat striatum and levels of serotonin (5-HT) and its metabolite in the medial prefrontal cortex, nucleus accumbens, striatum, anterior hypothalamus, amygdala and hippocampus. These decreases in DA, 5-HT and their metabolites were prevented by pretreatment with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, or D-CPP-ene (SDZ EAA 494), a competitive NMDA antagonist. The results suggest that NMDA receptors play a role for MA-induced serotonergic damage in various brain regions as well as dopaminergic damage in the striatum.
    Type of Medium: Electronic Resource
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