EFFECTS OF M-CHLOROPHENYLPIPERAZINE ON REGIONAL BRAIN GLUCOSE-UTILIZATION - A POSITRON EMISSION TOMOGRAPHIC COMPARISON OF ALCOHOLIC AND CONTROL SUBJECTS

m-Chlorophenylpiperazine (mCPP) is a mixed serotonin agonist/antagonis t used extensively in psychiatric research. Alcoholics show blunted ne uroendocrine responses to mCPP, and in some settings mCPP can induce c raving for alcohol, particularly among early onset alcoholics. We used 2-[F-18]-2-deoxy-D-glucose positron emission tomography to examine th e effects of intravenously administered mCPP (0.08 mg/kg) on brain glu cose utilization in a group of 18 male alcoholics and 12 healthy male control subjects. Differences between two sequential scans (the first followed placebo and the second followed mCPP) were evaluated statisti cally with a Gaussian random field-based method, Among healthy volunte ers mCPP significantly increased brain glucose metabolism in the right medial and posterior orbital gyrus, the cerebellar hemispheres bilate rally, the left nucleus accumbens, the head of the caudate nucleus bil aterally, the anterior and medial-dorsal nuclei of the thalamus bilate rally, the middle frontal gyrus, the left insular cortex, the left mid dle temporal gyrus, and the posterior cingulate gyrus. Among alcoholic subjects mCPP significantly increased brain glucose metabolism in lar ger areas of the cerebellum and posterior cingulate than it did in hea lthy volunteers, but compared with the healthy volunteers, alcoholics showed a smaller area of mCPP-induced activation in the thalamus, almo st no activation in the orbital cortices, and no activation at all in the head of the caudate nucleus or the middle frontal gyrus. These res ults suggest that a serotoninergic challenge activates basal ganglia c ircuits involving orbital and prefrontal cortices among healthy volunt eers but that the response of these circuits is blunted among alcoholi cs.