Contrasting responses by basal ganglia met-enkephalin systems to low and high doses of methamphetamine in a rat model

The influence of methamphetamine (METH) on basal ganglia met-enkephalin (Me nk) was studied by determining levels of this peptide in striatal, pallidal and nigral regions after administering a single low (0.5.mg/kg) or high (1 0 mg/kg) dose of this stimulant. The Menk levels in the striatal and pallid al areas were reduced and increased after the low- and high-dose METH treat ments, respectively, 12 h after drug administration in all striata[ and pal lidal regions examined. The tow-dose effect appeared to be principally infl uenced by increased activation of the dopamine D-2-like receptor, while the high-dose effect seemed to result from dominance of D-1-like receptor acti vation. However, both effects required coactivation of D-1- and D-2-like re ceptors. For the most part, both low- and high-dose METH-induced changes in Menk tissue content were fully recovered by 24 h. The Menk levels were not significantly altered in the substantia nigra 3-24 h after either METH tre atment. Results reported herein indicated that striatal and pallidal Menk p athways respond differently after acute treatment with low or high doses of METH.