In recent years, investigations into the biochemical pharmacology of ethanol have focussed on the role of tetrahydroisoquinoline (TIQ) alkaloids (which are condensation products of acetaldehyde, the primary metabolite of ethanol, with endogenous catecholamines) as possible mediators of the behavioral, autonomic and teratogenic effects of ethanol. Both in vitro and acute in vivo studies have demonstrated the biosynthesis of these TIQs in animals and in man. Speculations on the role of TIQs in the development of physical dependence to ethanol have received significant attention. This investigation will address itself to the following questions: (1) Are TIQs (salsolinol or tetrahydropapaveroline) formed in vivo under conditions of physical dependenct to alcohol, without specific pharmacolical manipulation of the experimental model? (2) Will inhibition of TIQ biosynthesis interfere with the development of physical dependence to ethanol? (3) Do TIQs cross the placental barrier or are they formed in the fetus to account for the teratogenicity of alcohol? The experimnts will be performed on mice and rats. Physical dependence to alcohol will be induced by the inhalation procedure, and TIQs will be measured in a variety of tissues including maternal brain and adrenal glands and fetal and placental tissues. BIBLIOGRAPHIC REFERENCES: O'Neill, P.J. & Rahwan, R.G.: Absence of formatin of brain salsolinol in ethanol-dependent mice. Journal of Pharmacoloty & Experimental Therapeutics 200: 306-313, 1977. O'Neill, P.J. & Rahwan, R.G.: A modified gas-chromatographic/electron capture assay for salsolinol in brain tissue. Journal of Pharmaceutical Sciences, in press, 1977.