Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters.

The effects of chronic estrogen treatment on radial arm maze performance and on levels of central monoaminergic and amino acid neurotransmitters were examined in ovariectomized (Ovx) rats. In an eight arms baited paradigm, choice accuracy was enhanced following 12 days but not 3 days of treatment. In addition, performance during acquisition of the eight arms baited maze task was better in estrogen-treated Ovx rats than in Ovx rats. Performance of treated rats was also enhanced in win-shift trials conducted 12 days postestrogen treatment. Working, reference, and working-reference memory was examined when four of the eight arms were baited, and only working memory was improved by estrogen and only after long-term treatment. Activity of Ovx rats on an open field, crossings and rearings, was increased at 5 but not at 35 days following estrogen treatment. In medial prefrontal cortex, levels of NE, DA, and 5-HT were decreased but glutamate and GABA levels were not affected following chronic estrogen treatment. Basal forebrain nuclei also showed changes in monoamines following estrogen. Hippocampal subfields showed no effects of estrogen treatment on monoaminergic or amino acid transmitters. Levels of GABA were increased in the vertical diagonal bands following chronic estrogen. Results show that estrogen enhances learning/memory on a task utilizing spatial memory. Effects in Ovx rats appear to require the chronic (several days) presence of estrogen. Changes in activity of both monoaminergic and amino acid transmitters in the frontal cortex and basal forebrain may contribute to enhancing effects of estrogen on learning/memory.