REGIONAL BRAIN METABOLIC RESPONSE TO LORAZEPAM IN ALCOHOLICS DURING EARLY AND LATE ALCOHOL DETOXIFICATION

Changes in GABA function have been postulated to be involved in alcoho l tolerance, withdrawal and addiction. In this study we measured regio nal brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission), in alcoholics during early and late withdrawal, Brain metabolism was meas ured using PET and 2-deoxy-2[F-18]fluoro-D-glucose after placebo (base line) and after lorazepam (30 mu g/kg intravenously) in 10 alcoholics and 16 controls, In the alcoholics evaluations were performed 2 to 3 w eeks after detoxification and were repeated 6 to 8 weeks later. Contro ls were also evaluated twice at a 6 to 8 weeks interval, While during the initial evaluation metabolism was significantly lower for most bra in regions in the alcoholics than in controls in the repeated evaluati on the only significant differences were in cingulate and orbitofronta l cortex, Lorazepam-induced decrements in metabolism did not change wi th protracted alcohol withdrawal and the magnitude of these changes we re similar in controls and alcoholics except for a trend towards a blu nted response to lorazepam in orbitofrontal cortex in alcoholics durin g the second evaluation, Abnormalities in orbitofrontal cortex and cin gulate gyrus in alcoholics are unlikely to be due to withdrawal since they persist 8 to 11 weeks after detoxification. The fact that there w as only a trend of significance for an abnormal response to lorazepam in orbitofrontal cortex indicates that mechanisms other than GABA are involved in the brain metabolic abnormalities observed in alcoholic su bjects.