REGIONAL BRAIN GLUCOSE-METABOLISM AFTER ACUTE ALPHA(2)-BLOCKADE BY IDAZOXAN

Background: Several classes of antidepressant drugs act on alpha(2)-ad renergic receptors. Studies of patients with disorders responsive to t reatment with these drugs report group differences in ex vivo measures of alpha(2)-binding and in vivo responses mediated by alpha(2)-recept ors. Measurement of regional brain metabolic response to an alpha(2)-a ntagonist may be a useful method for further definition of the role al pha(2)-receptor regulation plays in the treatment of neuropsychiatric disorders. Methods: Regional brain glucose metabolism was measured bef ore and after infusion with 200 mu g/kg idazoxan with use of F-18-fluo ro-2-deoxyglucose positron emission tomography in 13 healthy men. Arte rial drug concentration, behavioral responses, and cardiovascular resp onses were also measured. Results: The absolute and normalized glucose metabolic rate significantly increased in primary visual cortex. Sign ificant increases and decreases occurred in normalized metabolic rates in prefrontal cortical regions. Measurement of metabolic effects occu rred during the peak cardiovascular response. Conclusions: Our finding s are consistent with regionally specific effects of alpha(2)-blockade . This method may be useful for the study of alpha(2)-receptor functio n in humans.