Age-dependent differential responses of monoaminergic systems to high doses of methamphetamine

Abuse of methamphetamine (METH) by adolescents is a major public health iss ue in the U.S.A. Because of the neurotoxic potential of METH, we examined t he response of CNS monoaminergic systems in young (adolescent) animals [pos tnatal day (PND) 40] to high-dose treatments (10 mg/kg, four injections, 2- h intervals) of this drug and contrasted these effects to those seen in old er (young adult) rats (PND 90). Consistent with previous reports, we observ ed that PND 40 animals did not manifest the long-term (7-day) deficits in e xtrapyramidal dopamine (DA) parameters observed in PND 90 rats. In contrast , METH-induced rapid (1-h) reduction in the activity of striatal DA transpo rters occurred in both age groups. In addition, both persistent (7-day) and rapid (1-h) deficits in serotonergic systems (measured as reductions in tr yptophan hydroxylase activity) were observed in PND 40 and 90 rats. Age-rel ated differences in METH-induced hyperthermia did not appear to be a princi pal cause for our observations; however, age-dependent pharmacokinetics of this drug might have contributed to the differential METH monoaminergic res ponses by PND 40 and 90 animals.