BDNF INCREASES MONOAMINERGIC ACTIVITY IN RAT-BRAIN FOLLOWING INTRACEREBROVENTRICULAR OR INTRAPARENCHYMAL ADMINISTRATION

We have previously demonstrated alterations in serotonin metabolism wi thin descending pathways following infusion of brain-derived neurotrop hic factor (BDNF) into the midbrain, near the periaqueductal gray and dorsal and median raphe nuclei. The aim of the present study was to ex tend these studies to include a comprehensive regional examination of monoamine (serotonin, dopamine and norepinephrine) and metabolite leve ls in discrete areas of the intact, adult rat forebrain following dire ct intraparenchymal midbrain BDNF infusion. We have compared neurochem ical changes following midbrain infusion of BDNF to those obtained fol lowing intracerebroventricular (i.c.v.) infusion. Significant increase s in levels of 5-HIAA and/or the 5-HIAA/5-HT ratio were found in all a reas examined including the hippocampus, cortex, striatum, n. accumben s, substantia nigra and hypothalamus following both midbrain and i.c.v . infusion. Changes in dopaminergic activity were also observed, but d isplayed more regional specificity, i.e. changes were found primarily within the striatum and cortex. The two infusion sites produced simila r patterns of neurochemical effects although the magnitude of the chan ges did vary in some areas. These results suggest that BDNF increased synthesis and/or turnover of serotonin, and to a lesser extent dopamin e, in the mature rat forebrain. Furthermore, these data point to possi ble functional roles for BDNF in neuropsychiatric and neurodegenerativ e conditions which involve a dysregulation of these monoamine systems.