536 Brahl Research, 194 (1980) 536 539 (5 Elsevier/North-Holland Biomedical Press The effect of specific brain lesions on the high affinity binding of GABA in the substantia nigra MARK J. KUPERSMITH and ABRAHAM N. LIEBERMAN Department of Neurology, New York University Medical Center, 550 First Avenue, New York, N. g. 10016 (U.S.A.) (Accepted April 3rd, 1980) Key words: GABA binding -- brain lesions -- substantia nigra -- 6-hydroxydopamine The substantia nigra is innervated by a descending striato-pallidal GABAergic pathway. Experimentally induced lesions suggest the origin of these GABAergic con- nections maybe in the striatum, globus pallidus or both t0,11. Dopaminergic and non- dopaminergic neurons in the substantia compacta and substantia reticulata receive these afferents with a heterogenous distribution2 Alteration of neuronal activity a,3,s and motor behavior la,18 occurs with microinjection of GABA, GABA agonists, or GABA antagonists into the substantia nigra. Thus, a functional GABAergic synapse with a specific GABA receptor is probably present in the substantia nigra4,~a. In this presentation we report the effect of lesions in specific brain regions on the binding characteristics of GABA to its receptor in the substantia nigra. Male Sprague-Dawley rats weighing 150-170 g were employed for the study. Surgery was conducted under chloral hydrate-ether anesthesia in the standard Kopf stereotaxic device. Unilateral electrolytic lesions, using a Teflon-coated stainless- steel wire, were made with 1 mA current for 30 sec in the globus pallidus (A 6.5, L 2.4, H --0.8) or the crus cerebri (A 3.75, L 2.2, H --2.6) according to the atlas of K6nig and KlippeP 2. Unilateral destruction of the nigral dopaminergic cells was performed by injection of 6-hydroxydopamine (4 #g free base in 3/A chilled 0.9 ~ NaCI and 0.1 ~ ascorbic acid) over a 3 rain interval into the medial forebrain bundle (A 3.2, L 1.4, H 2.8). After 10 days the 6-hydroxydopamine (6-OHDA)-injected rats were tested for contralateral rotation following i.p. injection of apomorphine 0.5 mg/kg (chilled 0.9~ NaC1 and 0.1 ~ ascorbic acid). In separate experiments animals with effective lesions had depleted stores of dopamine in the ipsilateral striatum by at least 80%. Only those 6-OHDA-treated animals demonstrating this rotation were considered effectively dopamine depleted. The animals were sacrificed by cervical fracture at 1 and 21 days after lesioning and the brains were dissected on ice. Whole substantia nigra or substantia reticulata lateralis and substantia compacta were removed from coronal sections on a freezing microtome.