Life Sciences, Vol. 36, pp. 309-314 Pergamon Pres~ Printed in the U,S.A. SALSOLINOL AND DOPAMINE IN RAT MEDIAL BASAL HYPOTHALAMUS AFTER CHRONIC ETHANOL EXPOSURE Wendy D. Myers, Lorraine Mackenzie, Kim T. Ng, George Singer, George A. Smythe* and Mark W. Duncan* Department of Psychology and Brain-Behaviour Research Institute, La Trobe University, Bundoora, Australia, 3083 *Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia, 2010 (Received in final form November 9, 1984) Summary Endogenous levels of salsolinol and dopamine were measured by a gas chromatography/mass spectrometry (GC/MS) - selected ion monitoring technique using deuterated internal standards in Long Evans rats chronically exposed to ethanol for ten months. Chronic ethanol exposure produced significant increases of dopamine and salsolinol concentrations in the medial basal hypothalamus but not striatum. The data suggest that the occurrence of salsolinol in rat brain tissue is a consequence of an in vivo Pictet-Spengler cyclization. For over a decade interest has been directed toward proposals suggesting the involvement of Pictet-Spengler condensation products in the etiology of alcohol addiction (1,2). The possibility that these products might be formed following alcohol consumption by a condensation between a monoamine and an aldehyde, in particular acetaldehyde, remains controversial (3,4). The most studied of all Pictet-Spengler condensation products is salsolinol (l-methyl-6,7-dihydroxy- 1,2,3,4-tetrahydroisoquinoline), the product of a direct cyclization between dopamine and acetaldehyde (3,5). Salsolinol has been reported in a variety of food sources including cocoa (6), bananas (7), beer and port (8). These findings suggest that diet must, therefore, be considered a potentially important source of salsolinol (3). Salsolinol has been shown to block central dopaminergic mechanisms in the rat and to act as a potent stimulus for prolactin release (9). Endogenous salsoli- nol has been reported in the brain of neonatal rats (i0) and in medial basal hypothalami of adult ma]e Wistar rats (9). The presence of salsolinol has been shown in urine (ii) and cerebrospinal fluid (12,23) of both alcoholics and nonalcoholics. The urinary level of salsolinol was found to be significantly higher in alcoholics than in the nonalcoholic subjects (12,13). More recently, Sjoquist, Liljequist and Engel (14) reported a significant increase of salsoli- nol concentrations in dopamine-rich brain areas (striatum and limbJc forebrain) of male Sprague-Dawley rats chronically exposed to ethanol as their sole drink- ing fluid for 150 days. This finding led us to consider the possibility that rats of a different strain, chronically exposed to ethanol, may show increased sa]solinol levels in another anatomical region of the brain implicated in sal- solinol formation, ie., the medial basal hypothalamus (9). 0024-3205/85 $3.00 + .00 Copyright (c) 1985 Pergamon Press Ltd.