BEHAVIORAL RESPONSITIVITY TO DOPAMINE-RECEPTOR AGONISTS AFTER EXTENSIVE STRIATAL DOPAMINE LESIONS DURING DEVELOPMENT

Dopamine (DA) receptor responsitivity was investigated in adult rats t hat received intrastriatal (i.s.) injections of 6-OHDA (20 mu g pel st riatum) on day of birth or postnatal Day 1 (Day 0/Day I). Neonatally l esioned rats exhibited self-biting behavior and increases in stereotyp ic gnawing following treatment with the mixed D1/D2 receptor agonist a pomorphine (0.32-3.2 mg/kg) or the DI-like receptor agonist SKF38393 ( 10 mg/kg). increases in locomotor activity, rearing, and paw treading were also observed in the lesioned rats after SKF38393 (1-10 mg/kg) tr eatment. The incidences of the prototypical D1 receptor-mediated behav iors, grooming and abnormal perioral movements (i.e., oral dyskinesias ) were not increased in the lesioned rats. However; the low dose (0.32 mg/kg) of apomorphine as well as all doses of the D2-like receptor ag onist quinpirole (0.32-3.2 mg/kg) induced grooming in the lesioned mts , which was not observed in nonlesioned cona ol mts. Autoradiographs o f [H-3]mazindol binding to high affinity DA uptake sites revealed an e xtensive loss of DA terminals in the striata of the neonatally lesione d rats. These data suggest that near-total (greater than or equal to 9 5%) DA depletions on Day 0/Day 1 result in long-term alterations in th e functional sensitivity of DA receptors, as well as possible changes in the interactions between D1 and D2 receptors. Comparisons of these results with those seen following lesions of the early-developing DA s ystem (''patch-selective'' lesions) and lesions made at other time poi nts will be discussed. (C) 1998 John Wiley & Sons, Inc.