Methamphetamine (MA) increases extracellular dopamine (DA) and at chronic high doses induces toxicity as indicated by decreased expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT). Notably, rats will self-administer MA... more
Methamphetamine (MA) increases extracellular dopamine (DA) and at chronic high doses induces toxicity as indicated by decreased expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT). Notably, rats will self-administer MA in escalating quantities producing such toxicity. However, the impact of MA at sub-toxic doses on DA regulation is not well established. The temporal dynamics of DA regulation following cessation of sub-toxic escalating and binge doses of non-contingent MA were investigated as changes therein may be associated with escalation of MA intake. MA was administered 3×/day using an established 14-day escalating-dose regimen (0.1-4.0 mg/kg) or a single-day binge-style administration (3 × 4 mg/kg). DA tissue content, DA turnover, TH protein, TH phosphorylation, DAT, and vesicular monoamine transporter 2 were measured in nigrostriatal and mesoaccumbens pathways 48 h and 2 weeks after MA cessation. Changes in striatal DA regulation were limited to increased DA...
