CHRONIC CONTINUOUS AND INTERMITTENT L-3,4-DIHYDROXYPHENYLALANINE TREATMENTS DIFFERENTIALLY AFFECT BASAL GANGLIA FUNCTION IN 6-HYDROXYDOPAMINE LESIONED RATS - AN AUTORADIOGRAPHIC STUDY USING [(3)H]FLUNITRAZEPAM

The effects of chronic 'continuous' and 'intermittent' L-3,4-dihydroxy phenylalanine treatments on GABA receptor function in the basal gangli a of rats with unilateral 6-hydroxydopamine lesions of the medial fore brain bundle was investigated, by autoradiography with [H-3]flunitraze pam. The 6-hydroxy-dopamine lesion itself, increased [H-3]flunitrazepa m binding in the substantia nigra pars reticulata (+17%. with respect to intact side) and entopeduncular nucleus (+44%), but decreased bindi ng in the globus pallidus of the denervated hemisphere (-20%). 'Interm ittent' L-3,4-dihydroxyphenylalanine treatment reduced the [H-3]flunit razepam binding changes observed in the substantia nigra pars reticula ta (-13%) and entopeduncular nucleus (-4%), whereas 'continuous' infus ion of the same daily dose of L-3,4-dihydroxyphenylalanine had less ef fect (+14%, substantia nigra pars reticulata; +26%, entopeduncular nuc leus). In contrast, the [H-3]flunitrazepam binding decrease in the glo bus pallidus of the 6-hydroxydopamine lesioned animals was unaffected by either regime of chronic L-3,4-dihydroxyphenylalanine treatment. Th e changes in GABA receptor function implied by these results provide f urther insight into the pathophysiological effects of L-3,4-dihydroxyp henylalanine treatment on basal ganglia function, following dopamine d enervation. In accordance with existing electrophysiological and bioch emical evidence on this subject, the main implications of these result s include reduced GABA sensitivity of neurons in the entopeduncular nu cleus and substantia nigra pars reticulata, following chronic 'intermi ttent', but not chronic 'continuous' L-3,4-dihydroxyphenylalanine trea tment; this may be due to a reversal of the 6-hydroxydopamine induced decrease in the GABA-mediated neurotransmission in the striatoentopedu ncular and striatonigral pathways. In contrast, the regulation of GABA receptors in the globus pallidus does not appear to be subject to mod ulation by chronic L-3,4-dihydroxyphenylalanine administration, sugges ting that dopamine replacement in this manner does not modify the 6-hy droxydopamine induced increase in GABA-mediated neurotransmission in t he stratopallidal pathway.