Effects of RU 52583, an α2-antagonist, on Memory in Rats With Excitotoxic Damage to the Septal Area

• Published in: Pharmacology, biochemistry and behavior Vol. 56; no. 4; pp. 649 - 655
• Main Authors: M'Harzi, M, Willig, F, Bardelay, C, Palou, A.-M, Oberlander, C
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.04.1997
• Subjects: Adrenergic receptors; Cholinergic; Hippocampal theta; Memory impairments; Radial maze; Rat; Radial maze; Adrenergic receptors; Hippocampal theta; Rat; Cholinergic; Memory impairments
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(96)00422-4

The anti-amnesic action of RU 52583, an α2-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 α2-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 α2-adrenergic antagonist RU 52583 possesses cognition-enhancing properties in rats with damage to the septohippocampal system.