Dopamine receptors and sensorimotor behavior in MPTP-treated mice

Abstract

The contributions of dopamine (DA) receptor subtypes to sensorimotor behavior was studied in MPTP-treated mice. All DA antagonists studied produced akinesia and catalepsy in control and MPTP-treated mice. The rank order of potency was haloperidol > SCH 23390 > > l-sulpiride . Combined subthreshold doses of SCH 23390 and l-sulpiride induced marked motor impairments. Dose-response curves for each drug were shifted to the left in the MPTP-treated mice, suggesting behavioral supersensitivity. Pretreatment with the selective D 1 agonist SKF 38393 or the selective D 2 agonist quinpirole either alone or in subthreshold combination also prevented cold swim-induced motor deficits in the MPTP-treated animals. Haloperidol and SCH 23390 also produced somatosensory neglect in both control and MPTP-treated mice, with haloperidol > SCH 23390. Again, a shift of the dose-response curves to the left was observed in the MPTP-treated animals. l-Sulpiride, or another D 2 antagonist spiperone, had only minimal effects on somatosensory orientation in both control and MPTP-treated mice. Our studies suggest that both D 1 and D 2 receptors participate in the expression of motor behavior, while D 1 receptors appear to be predominantly responsible for somatosensory orientation.