Abekawa T, Ohmori T, Koyama T. Effects of repeated administration of a high dose of methamphetamine on dopamine and glutamate release in rat striatum and nucleus accumbens. Brain Res 643: 276-281

Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan.
Brain Research (Impact Factor: 2.84). 05/1994; 643(1-2):276-81. DOI: 10.1016/0006-8993(94)90033-7
Source: PubMed


We examined effects of a high dose of methamphetamine (MA) (4.02 mg free base/kg, s.c., at 2-h intervals, 4 injections) on extracellular concentrations of monoamines such as dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) and those of glutamate and other several amino acids in rat striatum (ST) and nucleus accumbens (NA) using in vivo microdialysis. Five days after the microdialysis, tissue concentrations of monoamines were measured. The toxic dose of MA markedly increased extracellular concentrations of DA, and decreased those of DOPAC, HVA and 5-HIAA in both ST and NA. Magnitude of the increase in DA release was not different between ST and NA. Extracellular concentrations of glutamate showed a gradual increase in ST, but not in NA, while other amino acids showed no changes in both ST and NA. Tissue concentrations of serotonin (5-HT) and 5-HIAA were decreased to 43-58% of control values in both ST and NA, whereas those of DA, DOPAC and HVA showed 43-54% decrease in ST but no changes in NA. These data suggest that the marked increase of DA release is not directly related to the MA-induced dopaminergic neurotoxicity. The increase in glutamate release found only in ST may be related to the dopaminergic damage in ST. It may be that enhanced release in DA and glutamate act synergistically to cause the dopaminergic neurotoxicity in ST. However, enhancement in glutamate release did not appear to be essential for the MA-induced serotonergic neurotoxicity.

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    • "e l s e v i e r . c o m / l o c a t e / s c h r e s afferent transmission of the MPFC to the VTA (Abekawa et al., 1994; Cador et al., 1999; Peterson et al., 2000; Bjijou et al., 2002; Han et al., 2012). Clinical in vivo neuroimaging studies have attempted to add to the pre-clinical (animal) data with respect to the Glu hypothesis, using proton magnetic resonance spectroscopy ( 1 H MRS) in populations of schizophrenia and abstinent METH-addicted adults. "
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    ABSTRACT: Acute symptoms of methamphetamine-induced psychosis are similar to those of primary schizophrenia. Understanding similarities or differences in the biological substrate of these psychoses could lead to early differentiation of these two clinical conditions resulting in more efficient treatment strategies. Proton magnetic resonance spectroscopy was acquired from the medial prefrontal cortex in 29 unmedicated patients with first episode of psychosis (FEP), 29 abstinent methamphetamine-addicted people (METH) and 45 healthy controls (HCs) (age range 17.3 to 29.9years old). The METH group displayed robust reductions in concentration levels of glutamate (Glu) relative to FEP (Cohen's d=1.20) and HC (d=0.87). The METH group also displayed reduced levels of N-acetylaspartate (NAA) relative to FEP (d=0.53) and HC (d=0.76). The HC group displayed a positive association between levels of Glu and NAA, r(45)=0.52, p<0.001, while the two clinical groups failed to show this normal association. This suggests that the cellular metabolism is altered in both conditions. These data support the assumption that cellular abnormalities differ between primary schizophrenia and methamphetamine addiction despite the overlap in clinical presentation.
    Full-text · Article · Jun 2014 · Schizophrenia Research
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    • "These results were assumed to be caused by the difference between non-specific systemic CPP effects on the entire brain area, and aimed local efficacy in specific brain areas (Wolf, 1998), which was supported by the results of several other studies. For example, a gradual increase in extracellular concentrations of glutamate was found in striatum but not in NAc after a high dose of methamphetamine (Abekawa et al., 1994). An enhanced dopamine and glutamate efflux was also measured by in vivo microdialysis in the prefrontal cortex and striatum in rats sensitized with repeated methamphetamine treatment (Arai et al., 1996; Stephans and Yamamoto, 1995). "
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    ABSTRACT: Repeated administration of psychostimulants and other dependence-producing substances induces a substantial increase in behavioural responses, a phenomenon termed as behavioural sensitization. An increased response to the tested drug elicited by previous repeated administration of a different drug is called cross-sensitization. Behavioural sensitization is considered to be a relapse trigger in dependent subjects and animals sensitized by repeated administration of drugs of abuse, thus being considered a suitable model of craving, which is one of the very characteristic features of substance addiction. It has been described that apart from other actions, drugs of abuse exert their effect on the central nervous system by affecting glutamatergic transmissions, particularly via N-methyl-D-aspartate (NMDA) receptors. Thus, this review presents a brief overview of the impact of inhibition of NMDA receptor system on sensitization, reflecting particularly on behavioural sensitization to psychostimulants. The text combines up-to-date information with time-proven facts and also compares data from literature with the authors' recent findings concerning this topic.
    Full-text · Article · Mar 2014 · European journal of pharmacology
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    • "Methamphetamine acts on multiple classes of neurons as well as different molecular targets. In fact a variety of neurotransmitters are released under METH administration - namely, serotonin [66] glutamate [67-69] and acetylcholine [70, 71]. Among these, catecholamine neurons are considered as the main target since METH is a powerful DA and NE releaser [72, 73]. "
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    ABSTRACT: The activity of locus coeruleus (LC) neurons has been extensively investigated in a variety of behavioural states. In fact this norepinephrine (NE)-containing nucleus modulates many physiological and pathological conditions including the sleep-waking cycle, movement disorders, mood alterations, convulsive seizures, and the effects of drugs such as psychostimulants and opioids. This review focuses on the modulation exerted by central NE pathways on the behavioural and neurotoxic effects produced by the psychostimulant methamphetamine, essentially the modulation of the activity of mesencephalic dopamine (DA) neurons. In fact, although NE in itself mediates some behavioural effects induced by methamphetamine, NE modulation of DA release is pivotal for methamphetamine-induced behavioural states and neurotoxicity. These interactions are discussed on the basis of the state of the art of the functional neuroanatomy of central NE- and DA systems. Emphasis is given to those brain sites possessing a remarkable overlapping of both neurotransmitters.
    Full-text · Article · Jan 2013 · Current Neuropharmacology
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