1. Effects of RU 52583, an alpha 2-antagonist, on memory in rats with excitotoxic damage to the septal area.
- Author
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M'Harzi M, Willig F, Bardelay C, Palou AM, and Oberlander C
- Subjects
- Adrenergic alpha-Antagonists pharmacology, Animals, Choline metabolism, Cholinesterase Inhibitors pharmacology, Hippocampus metabolism, Hippocampus physiology, Idazoxan pharmacology, Male, Maze Learning drug effects, Muscarinic Agonists pharmacology, Physostigmine pharmacology, Rats, Theta Rhythm drug effects, Adrenergic alpha-2 Receptor Antagonists, Excitatory Amino Acid Agonists toxicity, Memory drug effects, N-Methylaspartate toxicity, Septal Nuclei drug effects, Vinca Alkaloids pharmacology
- Abstract
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. more...
- Published
- 1997
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