SENSITIVITY TO THE MOTORIC EFFECTS OF A DOPAMINE-RECEPTOR ANTAGONIST DIFFERS AS A FUNCTION OF AGE AT THE TIME OF DOPAMINE DEPLETION

The ability of the mixed D1/D2 dopamine (DA) receptor antagonist cis-f lupentixol to impair locomotor behavior in adult mts depleted of DA as weanlings was determined. Rats received lateral ventricular injection s of 6-hydroxydopamine (100-200 mu g/hemisphere) or its vehicle soluti on on postnatal Day 20, 27, or 35. We compared the ability of cis-flup entixol (.06, .25 and 1.0 mg/kg i.p.) to impair the initiation of volu ntary locomotion (i.e., akinesia) in control and DA-depleted subjects. Despite the fact that analyses of tissue homogenates revealed compara bly large (93-96%) depletions of striatal DA across the three ages, th e lesioned animals differed markedly in their sensitivity to the behav ioral effects of the receptor antagonist. Surprisingly, rats depleted of DA on Day 20 or 27 were no more sensitive than vehicle-treated cont rols to the akinesia-inducing effects of each dose of flupentixol. In contrast, rats depleted of DA on Day 35 were supersensitive to the eff ects of the drug as they exhibited akinesia after a low dose of flupen tixol 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 dam age. (C) 1997 John Wiley & Sons, Inc.