Presynaptic modulation of acetylcholine, noradrenaline, and serotonin release in the hippocampus of aged rats with various levels of memory impairments

Aged (25-27 months) Long-Evans female rats were distinguished according to whether they showed no significant impairment (AU), moderate impairment (AMI), or severe impairment (ASI) in a spatial reference-memory task. Young (3-5 months) rats served as controls. Electrically evoked overflow of tritium was assessed in hippocampal slices preloaded with [H-3]choline or [H-3]serotonin (5-HT). Nicotine-evoked overflow of tritium was measured after preloading with [H-3]noradrenaline (NA). Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity. and concentration of monoamines were assessed in homogenates. Aged rats exhibited reduced accumulation of [H-3]choline and [H-3]5-HT. increased accumulation of [H-3]NA, and weaker electrically evoked overflow of [H-3]acetylcholine ([H-3]ACh) and [H-3]5-HT. The overflow of [H-3]NA was not altered consistently by aging. Roughly, drugs acting presynaptically had comparable effects in aged rats: oxotremorine and CP 93.129 inhibited the overflow of [H-3]ACh, CP 93,129 and UK 14,304 reduced that of [H-3]5-HT. ChAT or AChE activity, and 5-HT concentration were not changed by age; NA concentration was reduced. When significant, changes were comparable in AU, AMI and ASI rats. Data show that aging alters cholinergic and serotonergic hippocampal innervations, release of ACh and 5-HT, but not presynaptic release-modulating mechanisms. These alterations do not account for variability in water-maze performance of aged rats. (C) 2003 Elsevier Science Inc. All rights reserved.