NEUROCHEMICAL, HISTOPATHOLOGICAL AND MNEMONIC EFFECTS OF COMBINED LESIONS OF THE MEDIAL SEPTAL AND SEROTONIN AFFERENTS TO THE HIPPOCAMPUS

Male Long-Evans rats received micro-injections of either N-methyl-D-as partate (NMDA) in the medial septum/vertical diagonal band (MS/DB), 5, 7-dihyroxytryptamine (5,7-DHT) in the fimbria/fornix and cingulate bun dle or combined NMDA/5,7-DHT micro-injections. NMDA administration cau sed considerable damage to the MS and enlarged the lateral ventricles. It reduced the activity of choline acetyltransferase as well as the i ntensity of acetylcholinesterase staining in the hippocampus. 5,7-DHT selectively reduced the concentration of hippocampal serotonin. The ra ts were assessed for spatial memory in the Morris water maze and the r adial arm maze (reference and working memory version). The 5,7-DHT-ind uced lesion of hippocampal serotonin had no effect by itself on either task. However, it augmented the reference memory impairment caused by the NMDA-induced lesion and delayed the recovery from NMDA-induced im pairment of working memory on the radial maze. Combined damage of hipp ocampal cholinergic and serotonergic afferents did not severely affect spatial memory.