DOES GFAP MESSENGER-RNA AND MITOCHONDRIAL BENZODIAZEPINE RECEPTOR-BINDING DETECT SEROTONERGIC NEURONAL DEGENERATION IN RAT

Intracerebroventricularly (ICV) injected 5,7-dihydroxytryptamine (5,7- DHT), which reduced by 70-90% forebrain serotonin levels, significantl y raised glial fibrillary acidic protein (GFAP) mRNA levels in the hip pocampus and nucleus raphe dorsalis 5 days but not 15 days after the l esion. A significant increase of mitochondrial benzodiazepine receptor s (MBR), measured by binding autoradiography of H-3-PK 11195, was foun d in the nucleus raphe dorsalis 5 and 15 days after the ICV 5,7-DHT an d also in the hippocampus, ventral tegmental area, and substantia nigr a at 15 days. No significant effect was observed in the striatum and c ortex for either GFAP mRNA or MBR binding. Unlike the ICV route, bilat eral injection of 5,7-DHT into the medial forebrain bundle, which caus ed a 65-90% reduction of serotonin levels in different forebrain regio ns, significantly raised GFAP mRNA and MBR binding only at the site of injection with no effect in hippocampus, striatum, and cortex. MBR bi nding slightly increased in the nucleus raphe dorsalis 15 days after t he lesion. High doses of d-fenfluramine (10 mg/kg intraperitoneally tw ice daily for 4 days) caused 80-90% reduction of serotonin levels 5 da ys after the last injection but did not change the GFAP mRNA or the MB R binding in any of the brain regions considered. These findings sugge st that the effect of 5,7-DHT on microglial and glial markers is proba bly related to a nonspecific interaction with other neuronal systems b esides the serotonin or to direct interaction with glial cells; the us e of these parameters for detecting selective degeneration of serotoni n axons presents some obvious limitations.