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

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.