Journal
NEUROTOXICOLOGY AND TERATOLOGY
Volume 32, Issue 3, Pages 346-355Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ntt.2010.01.006
Keywords
Dopamine; Serotonin; Neostriatum; Hyperthermia; Locomotor activity; Spatial learning; Allocentric learning; Acoustic startle; Egocentric learning; Neurotoxicity; GFAP; Novel object recognition
Categories
Funding
- NIH [DA006733]
- Scottish Right Fellowship and training grant [ES07051]
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Rationale: In rats, neurotoxic doses of methamphetamine (MA) induce astrogliosis, long lasting monoamine reductions, reuptake transporter down-regulation, and learning impairments. Objective: We tested whether comparable effects occur in C57BL/6 mice. Method: C57BL/6 mice were treated with 10 mg/kg s.c. x 4 MA on a single day and evaluated at various intervals thereafter. Results: The neurotoxic dose regimen of MA caused the predicted acute hyperthermia and increased striatal glial fibrillary acidic protein and reduced neostriatal dopamine. The MA-treated mice were hypoactive 24 h later but not 48 h later. MA-treated mice also showed exaggerated initial hyperactivity after a pharmacological dose of MA used to stimulate locomotion followed by a later phase of hypoactivity compared to saline-treated mice. No differences were observed on learning or memory tests (novel object recognition, egocentric, or spatial learning/memory). MA-treated mice showed a trend toward increased prepulse inhibition but not baseline acoustic startle reactivity. After testing, MA-treated mice showed reduced neostriatal dopamine and increased basal plasma corticosterone. Conclusions: A neurotoxic/binge regimen of MA in mice that produces the typical pattern of neurotoxic changes to those seen in rats, results in few behavioral changes. This may limit the utility of C57BL/6 mice for modeling the cognitive and behavioral effects described in human MA users who show such changes even after prolonged abstinence. (C) 2010 Elsevier Inc. All rights reserved.
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