Brain Research, 151 (1978)339-352 339 © Elsevier/North-Holland Biomedical Press BIOCHEMICAL CHANGES ACCOMPANYING UNILATERAL 6-HYDROXY- DOPAMINE LESIONS IN THE RAT SUBSTANTIA NIGRA JUAN M. SAAVEDRA, PAULETTE E. SETLER and JOHN W. KEBABIAN* Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Md. 20014 and (P.E.S.) Smith, Kline and French Laboratories, Philadelphia, Pa. 19101 (U.S.A.) (Accepted December 8th, 1977) SUMMARY The biochemical consequences of a unilateral 6-hydroxydopamine injection into the substantia nigra of the rat brain were investigated. Projections of dopaminergic neurons from the A8-A9-A10 regions to a number of forebrain areas were confirmed. No innervation to the hypothalamus, including the median eminence, or to the brain stem, could be found with the present techniques. No destruction of serotonergic or GABAergic fibers could be demonstrated in the lesioned substantia nigra. Increases in glutamic acid decarboxylase activity were found restricted to the caudate and zona compacta of the substantia nigra ipsilateral to the lesion, indicating the possibility of a physiological interaction between GABAergic and dopaminergic systems. The neuroanatomical localization of the nigral dopamine-sensitive adenylate cyclase was also studied. No change in enzyme activity was found after destruction of a great proportion of the dopaminergic cells, suggesting that this enzyme has an extradopaminergic localization in the substantia nigra. INTRODUCTION The metabolism of catecholamines can be studied in many discrete brain areas by the use of sensitive enzymatic-isotopic microtechniques3,10,19AT, 4s and a precise neuroanatomical microdissection procedure13,42,48, 50. The intracerebral injection of the neurotoxin 6-hydroxydopamine can produce uni or bilateral destruction of specific catecholamine pathways 53. The combination of these techniques allowed the study of the anatomical projections, metabolism and functional roles of specific catecho- laminergic systems in the brain. We have focused our studies on the dopaminergic * Current address: Experimental Therapeutics Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Md 20014, U.S.A.