Sensitivity to the motoric effects of a dopamine antagonist differ as a function of age at the time of dopamine depletion

The ability of the mixed D1/D2 dopamine (DA) receptor antagonist cis-flupentixol to impair locomotor behavior in adult rats depleted of DA as weanlings was determined. Rats received lateral ventricular injections of 6-hydroxydopamine (100-200 μg/hemisphere) or its vehicle solution on postnatal Day 20, 27, or 35. We compared the ability of cis-flupentixol (.06, .25, and 1.0 mg/kg, i.p.) to impair the initiation of voluntary locomotion (i.e., akinesia) in control and DA-depleted subjects. Despite the fact that analyses of tissue homogenates revealed comparably large (93-96%) depletions of striatal DA across the three ages, the lesioned animals differed markedly in their sensitivity to the behavioral effects of the receptor antagonist. Surprisingly, rats depleted of DA on Day 20 or 27 were no more sensitive than vehicle-treated controls to the akinesia-inducing effects of each dose of flupentixol. In contrast, rats depleted of DA on Day 35 were supersensitive to the effects of the drug as they exhibited akinesia after a low dose of flupentixol that had no effect in any controls or animals depleted of DA at younger ages. These results suggest clear age-dependent differences in the plasticity of residual striatal DA neurons following subtotal damage.