Serotonergic lesion of median raphe nucleus alters nerve growth factor content and vulnerability of cholinergic septohippocampal neurons in rat

About 45% of the serotonergic raphe neurons are reported to express nerve g rowth factor (NGF) receptors. We therefore investigated whether selective s erotonergic lesions of the median or dorsal raphe nuclei are associated wit h changes in NGF protein levels of the brain and whether the loss of seroto nergic function alters the vulnerability of cholinergic septohippocampal ne urons. in adult rats the hippocampal NGF content changed in a biphasic way after lesion of the median raphe nucleus by 5,7-dihydroxytryptamine (5,7-DH T), with a significant increase after 2-3 weeks of up to 35%, followed by a significant reduction of 22% below control levels after 7 weeks, and a ret urn to control levels within the following 4 weeks. By contrast, the decrea se in hippocampal serotonin and 5-hydroxyindoleacetic acid remained through out the observation period of 11 weeks, being still reduced to 15 and 30% o f the control levels, respectively. In the frontal cortex the partial loss of the serotonergic innervation projecting from the median raphe was associ ated 5 weeks after 5,7-DHT injection with an increase in NGF protein of 39. 7 +/-9.6% (P<0.05), which remained elevated up to 11 weeks. At 9 weeks afte r 5,7-DHT, the lesion of the septohippocampal cholinergic neurons induced b y the cholinotoxin ethylcholine aziridinium (AF64A) was exaggerated (P<0.05 ) as compared to AF64A-treated rats with intact serotonergic innervation. T he present data indicate that a serotonergic lesion of the median raphe nuc leus results in biphasic changes of NGF protein content and in a delayed in crease in the vulnerability of septohippocampal cholinergic neurons. (C) 20 01 Published by Elsevier Science B.V.