EFFECT OF SEX AND AGE ON BRAIN MONOAMINES AND SPATIAL-LEARNING IN RATS

The concentrations of noradrenaline (NA), dopamine (DA), serotonin (5- HT), and their metabolites were measured in the prefrontal cortex, cau date-putamen, and hippocampus in young (3 months) and aged (27-31 mont hs) Wistar rats of both sexes. Age-related changes were found in prefr ontal NA and HVA/DA ratio, striatal DA and DOPAC/DA ratio, and striata l and hippocampal 5-HT and 5-HIAA/5-HT ratio. Age and sex dependent ch anges were found in striatal DA and DOPAC/DA ratio, and hippocampal MH PG-SO4/NA ratio. The aged rats were tested in spatial discrimination a nd reversal tasks in a T maze. The effects of alpha(2)-agonist medetom idine (3 mu g/kg) on the task performance were assessed in relation to individual variation in monoamine metabolism. Medetomidine impaired s patial discrimination learning of the aged rats by interacting with th e hippocampal 5-HT turnover. Medetomidine improved reversal learning t hrough an interaction with the striatal DA turnover and reduced the nu mber of perseverative errors after reversal, mainly due to its interac tion with the prefrontal NA turnover. It is concluded that the memory enhancing effect of drugs acting through the brain monoamine systems i s highly dependent on the stage of degeneration of these systems that show considerable individual variation in aged animals.