Psychiatry Research: Neuroimaging, 50: 1-I 3 Elsevier 1 PET Analysis of ~“C~~lu~azanil Binding to Benrodiazepine Receptors in Chronic Alcohol-Dependent Men and Healthy Controls Jan-Eric Litton, Jack Neiman, Stefan Pauli, Lars Farde, Tomas Hindmarsh, Christer Halldin, and G&an Sedvall Received April 29, 1992; revised version received September 7, 1992; accepted November 23, 1992. zyxwvutsrqp Abstract. Benzodiazepine (BZ) receptor binding in the brain was determined in five chronic alcohol-dependent men and in five healthy male control subjects using [W]flumazenil (Ro 15-1788) and positron emission tomography (PET). Magnetic resonance imaging was used to evaluate brain anatomy and pathology, and to define regions of interest in the brain. [W]Flumazenil binding was quantified by applying a saturation procedure with two PET experiments, the first with high (400-3400 Ci/mmol) and the second with low (-1 Ci/mmol) specific radioactivity. Radioactivity in the pons was taken as an estimate of free and nonspecifically bound radioligand. Equilibrium was defined to prevail when the derivative of specific binding (dCb(t)/dt) was equal to zero. The values were used in a Scatchard analysis for determination of the maximum density of binding sites (I&,,) and the equilibrium binding constant (Kd). The mean values of hax and & were about the same in the two groups, but the B,,,,, variance for the alcoholics was significantly greater for all regions of interest as compared with the healthy volunteers. The results may indicate that chronic alcohol consumption has multiple effects on the BZ receptor complex. Key Words. Positron emission tomo~aphy, magnetic resonance imaging, Ro 15 1788, alcohol withdrawal. Chronic alcohol consumption has many effects on the structure and the function of the human brain (Ron, 1977; Neiman and Carlen, 1989). Abnormalities of ~nzodiazepine (BZ) receptor function may be related to the development of alcoholism or be the result of prolonged heavy drinking (Allan and Harris, 1986). The BZ receptor antagonist [ICJflumazenil has been shown to be a suitable ligand for positron emission tomographic (PET) analysis of BZ receptor binding in the human brain (Maziere et al., 1983; Persson et al., 1985, 1989a; Samson et al., 1985; Shinotoh et al., 1986; Iyo et al., 1991). Flumazenil has a short half-life and is rapidly Jan-Eric Litton, Ph.D., is Associate Professor, Department of Psychiatry and Psychology, and Deoartment of Clinical Neurouhvsioloav. Karolinska Institute. Jack Neiman. M.D.. Ph.D.. is Associate Professor, Department of Cl&& Al&%01 and Drug Addiction Research, I&olinska Ins&e. Stefan Pauli, M.D., MSc. in Eng. Physics, is from the Department of Psychiatry and Psychology, Karolinska Institute. Lars Farde, M.D., Ph.D., is Associate Professor, Department of Psychiatry and Psychology, Karolinska Institute. Tomas Hindma~h, M.D., Ph.D., is Associate Professor, Department of Neuroradiology, Karolinska Institute. Christer Halldin, Ph.D., is Associate Professor, -Department Psvchiatrv and Psvcholoev. Karolinska Institute. Gijran Sedvall, M.D.. Ph.D., is Professor. Deoartment of-Psychfatry ani Psychology, Karolinska Institute. (Reprint ‘requests to Dr. J.-E. Litton, -Dept. of Psychiatry and Psychology, Karolinska Hospital, S-104 01, Stockholm, Sweden.) 0165-1781/93/$06.00 @ 1993 Elsevier Scientific Publishers Ireland Ltd.