Effects of RU 52583, an alpha 2-antagonist, on memory in rats with excitotoxic damage to the septal area.
The anti-amnesic action of RU 52583, an alpha 2-adrenergic receptor antagonist, was evaluated through performance of spatial tasks in a radial maze by rats with N-methyl-D-aspartic acid (NMDA) lesion of the medial septal (MS) nuclei. Memory performance of lesioned or sham-operated rats was evaluated by measuring reference memory as long-term maintenance of an acquired performance and working memory or memory for recent events. The lesion: a produced significant impairments of the animals' memory performance, b) significantly reduced the sodium-dependent high-affinity choline uptake in the hippocampal formation, and c) deeply disrupted cholinergic hippocampal theta waves. Oral administration of RU 52583 at 1 and 2 mg/kg (tested doses: 1-5 mg/kg) prior to performance of the task markedly reduced memory impairments, whereas idazoxan, another alpha 2-adrenergic receptor antagonist, had no effect at tested doses (2-5 mg/kg). Cholinergic drugs--arecoline at 0.1 and 1 mg/kg (tested doses: 0.05-1 mg/kg) and physostigmine at 0.02 and 0.1 mg/kg (tested doses: 1, 2, and 5 mg/kg)-administered intraperitoneally showed a tendency to alleviate memory deficits. The present results show that the alpha 2-adrenergic antagonist RU 52583 possesses cognition-enhancing properties in rats with damage to the septohippocampal system.
M'Harzi
M
M
Centre de Recherches Roussel UCLAF, Romainville, France. mharzi@mac.rousseluclaf.fr
Willig
F
F
Bardelay
C
C
Palou
A M
AM
Oberlander
C
C
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002794:Choline / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D019329:Idazoxan / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D018721:Muscarinic Agonists / Q000494:pharmacology; D016202:N-Methylaspartate / Q000633:toxicity*; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D012686:Septal Nuclei / Q000187:drug effects*; D013826:Theta Rhythm / Q000187:drug effects; D014748:Vinca Alkaloids / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D002800:Cholinesterase Inhibitors; D018690:Excitatory Amino Acid Agonists; D018721:Muscarinic Agonists; D014748:Vinca Alkaloids; C075611:11-methyl-20,21-dinoreburnamenine; D016202:N-Methylaspartate; D010830:Physostigmine; D002794:Choline; D019329:Idazoxan