Spatial reference- (not working- or procedural-) memory performance of aged rats in the water maze predicts the magnitude of sulpiride-induced facilitation of acetylcholine release by striatal slices.
Cluster analysis of water-maze reference-memory performance distinguished subpopulations of young adult (3-5 months), aged (25-27 months) unimpaired (AU) and aged impaired (AI) rats. Working-memory performances of AU and AI rats were close to normal (though young and aged rats differed in exploration strategies). All aged rats showed impaired procedural-memory. Electrically evoked release of tritium was assessed in striatal slices (preloaded with [(3)H]choline) in the presence of oxotremorine, physostigmine, atropine+physostigmine, quinpirole, nomifensine or sulpiride. Aged rats exhibited reduced accumulation of [(3)H]choline (-30%) and weaker transmitter release. Drug effects (highest concentration) were reductions of release by 44% (oxotremorine), 72% (physostigmine), 84% (quinpirole) and 65% (nomifensine) regardless of age. Sulpiride and atropine+physostigmine facilitated the release more efficiently in young rats versus aged rats. The sulpiride-induced facilitation was weaker in AI rats versus AU rats; it significantly correlated with reference-memory performance. The results confirm age-related alterations of cholinergic and dopaminergic striatal functions, and point to the possibility that alterations in the D(2)-mediated dopaminergic regulation of these functions contribute to age-related reference-memory deficits.
Cassel
Jean-Christophe
JC
Laboratoire de Neurosciences Comportementales et Cognitives, FRE 2855, CNRS-Université Louis Pasteur, IFR 37 Neurosciences, GDR CNRS 2905, Strasbourg, France. jean-christophe.cassel@psycho-ulp.u-strasbg.fr
Lazaris
Anelise
A
Birthelmer
Anja
A
Jackisch
Rolf
R
D000109:Acetylcholine / Q000378:metabolism*; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D066298:In Vitro Techniques; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D013469:Sulpiride / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D018721:Muscarinic Agonists; D009627:Nomifensine; D019257:Quinpirole; D010095:Oxotremorine; D013469:Sulpiride; D010830:Physostigmine; D000109:Acetylcholine