Methamphetamine-induced neurotoxicity alters locomotor activity, stereotypic behavior, and stimulated dopamine release in the rat

Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio 45267, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 11/1999; 19(20):9141-8.
Source: PubMed

ABSTRACT 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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Available from: Tanya Wallace, Aug 11, 2015
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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.
    Neurotoxicology and Teratology 03/2014; DOI:10.1016/ · 3.22 Impact Factor
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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.
    European Journal of Neuroscience 09/2013; 38(10). DOI:10.1111/ejn.12361 · 3.67 Impact Factor
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    • "One of the indicators of METH-induced neurotoxicity is a decrease in the tyrosine hydroxylase (TH) protein levels in the brain (Armstrong and Noguchi, 2004; Cadet et al., 2011; Fumagalli et al., 1998; O'Callaghan and Miller, 1994; Sonsalla et al., 1996; Wallace et al., 1999). Consistent with these reports, the noncontingent neurotoxic METH exposure produced signs of neurotoxicity as shown by a decrease in tyrosine hydroxylase (TH) protein levels in the cortex , hippocampus, and striatum of METH exposed animals (saline compared to METH exposed animals P<0.05) (Fig. 3, top panel) (Armstrong and Noguchi, 2004; Cadet et al., 2011; Fumagalli et al., 1998; O'Callaghan and Miller, 1994; Sonsalla et al., 1996; Wallace et al., 1999). "
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    ABSTRACT: Methamphetamine (METH) is a highly addictive and neurotoxic psychostimulant. Its use in humans is often associated with neurocognitive impairment. Whether this is due to long-term deficits in short-term memory and/or hippocampal plasticity remains unclear. Recently, we reported that METH increases baseline synaptic transmission and reduces LTP in an ex-vivo preparation of the hippocampal CA1 region from young mice. In the current study, we tested the hypothesis that a repeated neurotoxic regimen of METH exposure in adolescent mice decreases hippocampal synaptic plasticity and produces a deficit in short-term memory. Contrary to our prediction, there was no change in the hippocampal plasticity or short-term memory when measured after 14 days ofMETH exposure. However, we found that at 7, 14, and 21 days of drug abstinence, METH-exposed mice exhibited a deficit in spatial memory, which was accompanied by a decrease in hippocampal plasticity. Our results support the interpretation that the deleterious cognitive consequences of neurotoxic levels of METH exposure may manifest and persist after drug abstinence. Therefore, therapeutic strategies should consider short-term as well as long-term consequences of methamphetamine exposure. Synapse, 2012. © 2012 Wiley Periodicals, Inc.
    Synapse 05/2013; 67(5). DOI:10.1002/syn.21635 · 2.43 Impact Factor
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