Differential neurotensin responses to low and high doses of methamphetamine in the terminal regions of striatal efferents

Neurotensin is a neuropeptide associated with basal ganglia dopaminergic neurons. Because levels of neurotensin in striatal tissue are differentially affected by low or high doses of methamphetamine, we employed microdialysis to assess the dose-dependent effects of methamphetamine on neurotensin release from the terminals of striatonigral and striatopallidal neurons. A low (0.5 mg/kg), but not high (10 mg/kg), dose of methamphetamine significantly increased nigral extracellular levels of neurotensin. The low-dose effect on extracellular nigral neurotensin levels was blocked by pretreatment with either a dopamine D1 or D2 receptor antagonist. In the globus pallidus, only half of the animals demonstrated increased neurotensin release after the low dose of methamphetamine. These findings suggest that low and high doses of methamphetamine differentially affect the release of neurotensin from the terminals of striatonigral neurons and that both dopamine D1 and D2 receptor activation contributes to the low-dose methamphetamine effects in the substantia nigra.