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 [3H]choline or [3H]serotonin (5-HT). Nicotine-evoked overflow of tritium was measured after preloading with [3H]noradrenaline (NA). Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity, and concentration of monoamines were assessed in homogenates. Aged rats exhibited reduced accumulation of [3H]choline and [3H]5-HT, increased accumulation of [3H]NA, and weaker electrically evoked overflow of [3H]acetylcholine ([3H]ACh) and [3H]5-HT. The overflow of [3H]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 [3H]ACh, CP 93,129 and UK 14,304 reduced that of [3H]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.
Birthelmer
A
A
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Universität Freiburg, Neuropharmakologisches Labor, Hansastrasse 9A, D-79104 Freiburg, Germany.
Stemmelin
J
J
Jackisch
R
R
Cassel
J-C
JC
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D000068438:Brimonidine Tartrate; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D019329:Idazoxan / Q000494:pharmacology; D066298:In Vitro Techniques; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000378:metabolism* / Q000503:physiopathology; D008719:Methiothepin / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013550:Swimming; D014316:Tritium / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018721:Muscarinic Agonists; D011725:Pyridines; D011758:Pyrroles; D011810:Quinoxalines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014316:Tritium; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; D012701:Serotonin; D000068438:Brimonidine Tartrate; D008719:Methiothepin; D010095:Oxotremorine; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine; D009638:Norepinephrine; D019329:Idazoxan