It has recently been recognized that modifications in the activity of the noradrenergic sensitive adenylate cyclase system may be associated with a variety of psychiatric illnesses. Alterations in adrenergic receptors are thought to be involved in the pathogenesis of drug and alcohol intoxication and withdrawal. One method of estimating the function of receptors in brain and other organs is by use of peripheral models. In the case of the human leukocyte beta-adrenergic receptor, changes in the function of this receptor appear to parallel changes which occur in the beta-receptors of other organ systems, including heart and brain. The withdrawal syndrome which follows cessation of chronic alcohol or sedative-hypnotic drug use is characterized by a cluster of physiological signs and symptoms of increased adrenergic activity. It is hypothesized that modifications in beta-receptor function occur in man, which account for these physiological effects. My laboratory has been investigating the role of beta-adrenergic receptors in the acute response to alcohol and in the pathogenesis of the alcohol withdrawal syndrome. Beta-adrenergic receptor function is assessed by measurement of radioligand binding to leukocyte membranes and measurement of beta-agonist stimulated cyclic AMP formation in intact leukocytes. Ethyl alcohol, in vitro, was found to cause a dose department increase in isoproterenol- and prostaglandin-stimulated cyclic AMp production in human lymphocytes. This study will extend those findings by further examining the effect of other alcohols, methadone, sedative-hypnotic drug exposure on the leukocyte beta-adrenergic receptor, in vitro. In addition, beta-adrenergic receptor function will be followed over time in human undergoing alcohol, methadone or sedative-hypnotic drug withdrawal, and correlated with plasma norepinephrine levels, and the subjects' clinical state. Through this work we hope to examine the mechanism underlying alcohol and related drug intoxification and withdrawal, correlating changes at the level of a neurotransmitter receptor with clinical signs and symptoms seen in patients.
