Hyperthermic and lethal effects of methamphetamine: roles of dopamine D1 and D2 receptors.
Both human and animal studies suggest that hyperthermia contributes to the lethal effects of methamphetamine. To elucidate the roles of dopamine D1 and D2 receptors in methamphetamine-induced hyperthermia and lethal effects, we used D1 knockout (D1KO) mice, D2 knockout (D2KO) mice, and wild-type littermates. After the administration (i.p.) of a single dose of 30 mg/kg methamphetamine, no hyperthermic effect on body temperature was observed in D2KO mice, though there was a slight elevation in D1KO mice and a marked elevation in wild-type mice. Approximately 27% of the wild-type mice died after the administration, compared to only 7% of D1KO mice and 4% of D2KO mice. In conclusion, both D1 and D2 receptors play roles in the lethal toxic effects of methamphetamine, and mainly the D2 receptor is involved in the elevation of body temperature.
Ito
Miki
M
Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Numachi
Yohtaro
Y
Ohara
Arihisa
A
Sora
Ichiro
I
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000235:genetics; D005334:Fever / Q000139:chemically induced* / Q000235:genetics* / Q000401:mortality; D007928:Lethal Dose 50; D008694:Methamphetamine; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017447:Receptors, Dopamine D1 / Q000172:deficiency / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000172:deficiency / Q000502:physiology*; D013997:Time Factors
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D008694:Methamphetamine