STUDIES ON THE CELLULAR-LOCALIZATION OF BIOCHEMICAL RESPONSES TO CATECHOLAMINES IN THE BRAIN

Studies were undertaken to determine the cellular localization of the cyclic adenosine monophosphate (cAMP) response of various forebrain regions to beta-adrenoceptor stimulation. Using brain slices, it was found that the gliotoxin, fluorocitrate (FC), which blocks metabolism selectively in glial cells, virtually abolished the cAMP response to beta-receptor stimulation whereas the neurotoxin, kainic acid (KA), was without effect. FC was confirmed by electrophysiological recording to be selective for glial cells in the brain slices. Similar results were found for these agents on in vivo brain cAMP responses to beta-receptor stimulation using a new microdialysis technique to measure in vivo responses. It is concluded that the cAMP response to beta-adrenoceptor stimulation in various regions of the forebrain occurs predominantly in glia. To determine if this could be correlated with a second biochemical response to beta-receptor stimulation, preliminary studies were undertaken on the localization of the immediate early gene, c-fos, produced in the brain after in vivo stimulation of beta-receptors. It was found that unlike the cAMP responses the c-fos response to beta-receptor stimulation occurs predominantly in neurons. The possible relationship of these two responses is discussed.