Effects of toxic doses of methamphetamine (METH) on dopamine D1 receptors in the mouse brain

Methamphetamine (METH) is a drug of abuse that causes marked DA depletion in the mammalian dopaminergic systems. These are characterized by marked decreases in presynaptic markers including dopamine (DA) levels and DA transporters. Very little research has been carried out to evaluate possible postsynaptic effects of this drug. In the present study, we assessed the status of METH on striatal DA D1 receptors labeled with [H-3]SCH23390 after toxic doses of METH that were shown to cause marked depletion of various markers of presynaptic DA systems in mice [J. Neurochem. 69 (1997) 780]. Our results show that these doses of METH caused 30% decrease in striatal DA D1 receptors. In contrast, p53 knockout mice that show protection against the toxic effects of METH show no significant decreases in DA D1 receptors. These results suggest that toxic doses of METH that cause loss of presynaptic DA markers might also affect postsynaptic elements. We discuss the possibility that these changes might be secondary to toxic effects of METH on intrinsic striatal cell bodies. (C) 1998 Elsevier Science B.V.