3,4-DAP-evoked transmitter release in hippocampal slices of aged rats with impaired memory

Abstract

Based on a slice superfusion technique, this study investigated the release of acetylcholine, noradrenaline and serotonin in the hippocampus of aged rats (25–27 months) showing no or severe deficits in a spatial reference-memory task (water maze). Young adults (3–5 months) were used as controls. 3,4-diaminopyridine (3,4-DAP), a potassium channel antagonist which increases neuronal excitability, was used to evoke the overflow of the three neurotransmitters. The release of [ 3 H ]noradrenaline induced by stimulation of presynaptic nicotinic receptors was also assessed. The experiment compared the accumulation and 3,4-DAP-evoked (or nicotine-evoked) overflow of [ 3 H ] in hippocampal slices preincubated with [ 3 H ]choline, [ 3 H ]noradrenaline, or [ 3 H ]serotonin. In aged rats, only the accumulation of [ 3 H ]serotonin was reduced significantly (−17%). In percent of tissue-[ 3 H ], the 3,4-DAP-evoked overflow of [ 3 H ]serotonin was increased (+28%), and that of [ 3 H ]acetylcholine was reduced (−23%) in the aged rats. The nicotine-evoked overflow of [ 3 H ]noradrenaline was not altered in aged rats. There was a significant correlation of water-maze performance (distance to platform) and evoked overflow of [ 3 H ]serotonin. It is concluded that hippocampal cholinergic functions are more altered by aging than noradrenergic or serotonergic ones. Excessive excitability of serotonergic terminals, perhaps in addition to cholinergic dysfunction, might be a crucial factor accounting for age-related cognitive deficits in the present population of rats.