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Publication Detail

Title: Relationship between methamphetamine-induced dopamine release, hyperthermia, self-injurious behaviour and long term dopamine depletion in BALB/c and C57BL/6 mice.

Authors: Halladay, Alycia K; Kusnecov, Alexander; Michna, Lauri; Kita, Taizo; Hara, Chiaki; Wagner, George C

Published In Pharmacol Toxicol, (2003 Jul)

Abstract: Differential sensitivity to neurotoxic effects of methamphetamine on striatal dopaminergic neurones between C57BL/6 and BALB/c mice has been established. In the present studies, the interaction of methamphetamine-induced dopamine release, self-injurious behaviour, the neural immune response, and the long-term (3 day) dopamine depletion were examined in these strains after administration of 8 mg/kg methamphetamine. BALB/c mice showed increased hyperthermia compared to the C57BL/6 strain, as well as induction of interleukin-1beta. Additionally, homovanillic acid (HVA) levels, as well as HVA/DA turnover ratios were elevated in the striatum and frontal cortex of BALB/c mice, both compared to untreated mice and to the C57BL/6 strain after a single injection of methamphetamine. Pretreatment with acetaminophen eliminated the methamphetamine-induced hyperthermia in BALB/c mice and reduced body temperature in C57BL/6 mice. However, acetaminophen pretreatment did not affect any parameters of dopaminergic toxicity in the striatum or frontal cortex of the BALB/c strain following repeated methamphetamine injections. Furthermore, acetaminophen pretreatment did not alter the incidence of self-injurious behaviour in BALB/c mice. Therefore, hyperthermia and methamphetamine-induced toxicity appear to be independent phenomena while self-injurious behaviour may provide a better predictor of toxicity, which, in turn, may be related to dopamine release.

PubMed ID: 12828572 Exiting the NIEHS site

MeSH Terms: Actins/biosynthesis; Animals; Behavior, Animal/drug effects*; Cerebral Cortex/drug effects; Cerebral Cortex/metabolism; Corpus Striatum/drug effects; Corpus Striatum/metabolism; Dopamine/deficiency; Dopamine/metabolism*; Fever/chemically induced*; Injections, Subcutaneous; Interleukin-1/biosynthesis; Methamphetamine/adverse effects*; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Reverse Transcriptase Polymerase Chain Reaction; Self-Injurious Behavior/chemically induced*; Species Specificity

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