REGIONAL BRAIN METABOLIC RESPONSE TO LORAZEPAM IN SUBJECTS AT RISK FOR ALCOHOLISM

The mechanisms underlying the blunted response to alcohol administrati on observed in subjects at risk for alcoholism are poorly understood a nd may involve GABA-benzodiazepine receptors. The purpose of this stud y was to investigate if subjects at risk for alcoholism had abnormalit ies in brain GABA-benzodiazepine receptor function, This study measure d the effects of 30 mu g/kg (iv) of lorazepam, on regional brain gluco se metabolism using positron emission tomography and 2-deoxy-2[F-18]fl uoro-D-glucose in subjects with a positive family history for alcoholi sm (FP) (n = 12) and compared their response with that of subjects wit h a negative family history for alcoholism (FN) (n = 21). At baseline, FP subjects showed lower cerebellar metabolism than FN. Lorazepam dec reased whole-brain glucose metabolism, and FP subjects showed a simila r response to FN in cortical and subcortical regions, but FP showed a blunted response in cerebellum, Lorazepam-induced changes in cerebella r metabolism correlated with its motor effects. The decreased cerebell ar baseline metabolism in FP as well as the blunted cerebellar respons e to lorazepam challenge may reflect disrupted activity of benzodiazep ine-GABA receptors in cerebellum. These changes could account for the decreased sensitivity to the motor effects of alcohol and benzodiazepi nes in FP subjects.