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.
Halladay
Alycia K
AK
Joint Graduate Program in Toxicology, Rutgers University, Piscataway, NJ 08854, USA.
Kusnecov
Alexander
A
Michna
Lauri
L
Kita
Taizo
T
Hara
Chiaki
C
Wagner
George C
GC
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D005334:Fever / Q000139:chemically induced*; D007279:Injections, Subcutaneous; D007375:Interleukin-1 / Q000096:biosynthesis; D008694:Methamphetamine / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016728:Self-Injurious Behavior / Q000139:chemically induced*; D013045:Species Specificity
D000199:Actins; D007375:Interleukin-1; D008694:Methamphetamine; D004298:Dopamine