3,4-DAP-evoked transmitter release in hippocampal slices of aged rats with impaired memory.
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 [3H]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 [3H] in hippocampal slices preincubated with [3H]choline, [3H]noradrenaline, or [3H]serotonin. In aged rats, only the accumulation of [3H]serotonin was reduced significantly (-17%). In percent of tissue-[3H], the 3,4-DAP-evoked overflow of [3H]serotonin was increased (+28%), and that of [3H]acetylcholine was reduced (-23%) in the aged rats. The nicotine-evoked overflow of [3H]noradrenaline was not altered in aged rats. There was a significant correlation of water-maze performance (distance to platform) and evoked overflow of [3H]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.
Schweizer
Theresa
T
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Universität Freiburg, Neuropharmakologisches Labor, Hansastrasse 9A, D-79104 Freiburg, Germany.
Birthelmer
Anja
A
Lazaris
Anelise
A
Cassel
Jean-Christophe
JC
Jackisch
Rolf
R
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000109:Acetylcholine / Q000032:analysis; D000375:Aging / Q000502:physiology*; D000077770:Amifampridine; D000818:Animals; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000032:analysis / Q000378:metabolism*; D009638:Norepinephrine / Q000032:analysis; D009924:Organ Culture Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000032:analysis
D018377:Neurotransmitter Agents; D026902:Potassium Channel Blockers; D012701:Serotonin; D015761:4-Aminopyridine; D000109:Acetylcholine; D000077770:Amifampridine; D009638:Norepinephrine