Wallace TL, Gudelsky GA, Vorhees CV. Methamphetamine-induced neurotoxicity alters locomotor activity, stereotypic behavior, and stimulated dopamine release in the rat. J Neurosci 19: 9141-9148

Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio 45267, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 11/1999; 19(20):9141-8.
Source: PubMed


The neurochemical evidence of methamphetamine (MA)-induced toxicity to dopaminergic nerve terminals is well documented; however, the functional consequences are not clearly defined. The present study was designed to investigate whether MA-induced dopamine depletions affect locomotor activity, stereotypic behavior, and/or extracellular dopamine concentrations in the neostriatum. Male rats were treated with a neurotoxic regimen of MA (10 mg/kg, i.p., every 2 hr for four injections) or vehicle and tested for functional effects 1 week later. Animals that had received the neurotoxic regimen of MA showed a reduction in both caudate nucleus and nucleus accumbens dopamine contents of 56 and 30%, respectively. Furthermore, MA-treated rats exhibited a significant attenuation in spontaneous activity, as well as a significant diminution in MA (low dose)-stimulated locomotor activity as compared to vehicle-treated rats. However, there were no differences in the MA (low dose)-induced increases in extracellular dopamine concentrations in the caudate nucleus or the nucleus accumbens core of either group. Interestingly, the acute administration of higher doses of MA elicited a significantly augmented stereotypic response and a significantly attenuated increase in the extracellular concentration of dopamine in the caudate nucleus of rats treated with a neurotoxic regimen of MA as compared to vehicle-treated animals. These data indicate that MA-induced neurotoxicity results in abnormal dopamine-mediated behaviors, as well as a brain region-specific impairment in stimulated dopamine release.

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    • "This finding indicates that higher stereotyped behavior during withdrawal of METH may be due to dopaminergic depletion [7]. METH elicited an augmented stereotypic response and a decrease in the levels of dopamine in the caudate nucleus [32]. Whiles, EE improved the neuronal dysfunction due to Fig. 3. Effect of EE on anxiety-like behavior during spontaneous METH withdrawal in rats. "
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    ABSTRACT: This study was designed to examine the effect of environmental enrichment during METH administration on the behavioral withdrawal symptoms after drug abstinence in rats. Rats reared in standard (SE) or enriched environment (EE) during induction of METH dependence with bi-daily injections of METH (2mg/kg, at 12- hr. intervals) for 14 days. Then, rats were evaluated for behavioral withdrawal symptoms, and also for anxiety (Elevated plus maze-EPM) and depression (Forced swim test-FST) over a ten day period of abstinence. The results showed that stereotypic behaviors score and the number of rearing were significantly lower in METH/EE rats compared to the SE group during 1-4 days. Also, The METH/EE group exhibited more weight gain during 6-10 days of abstinence. The METH/EE rats exhibited lower levels of immobility after METH abstinence than control group in the FST. EE had no effect on anxiety-like behavior. This study showed that exposure to EE diminished the severity of withdrawal symptoms and depressive-like behavior during spontaneous withdrawal from METH. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Full-text · Article · Aug 2015 · Neuroscience Letters
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    • "Evidence from animal studies have revealed that prenatal administration of MA is toxic to dopaminergic and serotonergic neurons (Fuller and Hemrick-Luecke, 1992; Pu and Voorhees, 1993); and results in motor and learning impairment (Itoh et al., 1991; Slamberova et al., 2005; Wallace et al., 1999). Prenatal exposure in mice has been found to enhance conceptual DNA oxidation and lead to long-term and possibly permanent postnatal neurodevelopmental deficits in motor coordination (Jeng et al., 2005). "
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    ABSTRACT: Background Despite the evidence that women world-wide are using methamphetamine (MA) during pregnancy little is known about the neurodevelopment of their children. Design The controlled, prospective longitudinal New Zealand (NZ) Infant Development, Environment and Lifestyle (IDEAL) study was carried out in Auckland, NZ. Participants were 103 children exposed to MA prenatally and 107 not exposed. The Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development, Second Edition (BSID-II) measured cognitive and motor performance at ages 1, 2 and 3, and the Peabody Developmental Motor Scale, Second Edition (PDMS-II) measured gross and fine motor performance at 1 and 3. Measures of the child’s environment included the Home Observation of Measurement of the Environment and the Maternal Lifestyle Interview. The Substance Use Inventory measured maternal drug use. Results After controlling for other drug use and contextual factors, prenatal MA exposure was associated with poorer motor performance at 1 and 2 years on the BSID-II. No differences were observed for cognitive development (MDI). Relative to non-MA exposed children, longitudinal scores on the PDI and the gross motor scale of the PDMS-2 were 4.3 and 3.2 points lower, respectively. Being male and of Maori descent predicted lower cognitive scores (MDI) and being male predicted lower fine motor scores (PDMS-2) Conclusions Prenatal exposure to MA was associated with delayed gross motor development over the first 3 years, but not cognitive development. However, being male and of Maori descent were both associated with poorer cognitive outcomes. Males in general did more poorly on tasks related to fine motor development.
    Full-text · Article · Mar 2014 · Neurotoxicology and Teratology
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    • "The locomotor activity task used in the present study was conducted under redlight conditions to minimize the anxiogenic effects of a bright light (Bertoglio & Carobrez, 2002). Other studies (Robinson & Camp, 1987; Wallace et al., 1999) found a decrease in spontaneous locomotion after METH or D-amphetamine treatment using high-dose or neurotoxic regimens. However, the mechanisms that underlie this behavior have been difficult to identify. "
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    ABSTRACT: To better understand the neurobiology of methamphetamine (METH) dependence and the cognitive impairments induced by METH use, we compared the effects of extended (12 h) and limited (1 h) access to METH self-administration on locomotor activity and object place recognition, and on extracellular dopamine levels in the nucleus accumbens and caudate-putamen. Rats were trained to self-administer intravenous METH (0.05 mg/kg). One group had progressively extended access up to 12-h sessions. The other group had limited-access 1-h sessions. Microdialysis experiments were conducted during a 12-h and 1-h session, in which the effects of a single METH injection (self-administered, 0.05 mg/kg, i.v.) on extracellular dopamine levels were assessed in the nucleus accumbens and caudate-putamen compared with a drug-naive group. The day after the last 12-h session and the following day experimental groups were assessed for their locomotor activities and in a place recognition procedure, respectively. The microdialysis results revealed tolerance to the METH-induced increases in extracellular dopamine only in the nucleus accumbens, but not in the caudate-putamen in the extended-access group compared with the control and limited-access groups. These effects may be associated with the increased lever-pressing and drug-seeking observed during the first hour of drug exposure in the extended-access group. This increase in drug-seeking leads to higher METH intake and may result in more severe consequences in other structures responsible for the behavioral deficits (memory and locomotor activity) observed in the extended-access group, but not in the limited-access group.
    Full-text · Article · Sep 2013 · European Journal of Neuroscience
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