DOPAMINE D1 RECEPTOR BEHAVIORAL RESPONSITIVITY FOLLOWING SELECTIVE LESIONS OF THE STRIATAL PATCH COMPARTMENT DURING DEVELOPMENT

The behavioral effects of selective destruction of the dopamine (DA) input to the patch compartment of rat striatum early in development was investigated. Rat pups were given bilateral intrastriatal (i.s.) injections of the neurotoxin 6-hydroxydopamine (6-OHDA) on day of birth (P0) or postnatal day 1 (P1), which resulted in selective behavioral alterations following DA agonist treatment in adulthood. Neonatally-lesioned rats exhibited self-biting behavior following treatment with the DA precursor L-dihydroxyphenylalanine (L-DOPA). In response to treatment with the selective D1 agonist SKF38393, there was an increased of abnormal perioral movements. The cataleptogenic effects of the D1 antagonist SCH23390 and the D2 antagonist haloperidol were also studied. Neonatally-lesioned rats were significantly less cataleptic compared to control rats following D1 antagonist treatment, but not following D2 antagonist treatment. Autoradiographs of [H-3]mazindol binding to DA uptake sites (a measure of DA terminal density) showed a 'patchy' loss of approx. 40-50% in striatal tissue sections derived from the i.s. lesioned rats. These data suggest that injections of 6-OHDA into the striatum during this early postnatal period cause a DA lesion that results in long-term effects on a D1 receptor system.