Methamphetamine-induced behavioural effects and brain concentrations of methamphetamine and its metabolite amphetamine in mice.

(+)-Methamphetamine (MA) produced dose-related behavioural changes in mice. There was a correlation between the type of behavioural response and the peak brain MA concentration after the i.p. administration of each of the following doses of (+)-MA: 0.64 mg/kg (decreased quiescence--0.738 microgram/g MA), 2.5 mg/kg (increased locomotor activity--3.148 microgram/g MA) and 10.0 mg/kg (stereotyped behaviour--12.608 microgram/g MA). During the 90-min experimental period, there was no positive correlation between the magnitude of each type of drug-induced behaviour and the brain MA concentration. For 10.0 mg/kg (+)-MA, there was a negative correlation between the drug-induced stereotyped behaviour and the brain MA concentration. The apparent disappearance half-life of MA from brain was dependent on the dose of (+)-MA: 0.64 mg/kg (t1/2 56.6 min), 2.5 mg/kg (t1/2 66.6 min), 10.0 mg/kg (42.2 min). For the three (+)-MA doses, the metabolite amphetamine (A) also was present in the brain and the A/MA + A brain concentration ratio was 0.11--0.14. This metabolite appeared to have only a small involvement in the MA-induced behavioural effects.