Résumé
1.
1. Although the physical nature of sigma (σ) receptors have not yet been fully defined, several classes of selective ligands have been characterised, demonstrating a plethora of physiological actions. In the present review, the authors have set out to highlight two important aspects of the biological activities of σ ligands, their neuroprotective and anti-amnesic effects.
2.
2. The σ ligands present a therapeutic potential as neuroprotective agents in brain ischemia. The neuroprotective activity of many non-selective σ ligands is primarily a result of their affinity for the NMDA receptor complex. However, selective σ ligands are also neuroprotective, possibly by inhibition of the ischemic-induced presynaptic release of excitotoxic amino acids.
3.
3. The σ
1 ligands prevent the experimental amnesia induced by muscarinic cholinergic antagonists at either the learning, consolidation or retention phase of the mnesic process. This effect involves a potentation of acetylcholine release induced by σ
1 ligands selectively in the hippocampal formation and cortex.
4.
4. The σ
1 receptor ligands also attenuate the learning impairment induced by dizocilpine, a non-competitive antagonist of the NMDA receptor, and may relate to the potentiating effect of σ
1 ligands on several NMDA receptor-mediated responses previously described in vitro and in vivo in the hippocampus. This effect is shared by NPY- and CGRP-related peptides and by neuroactive steroids, confirming the in vitro evidences of functional interactions between the σ
1 receptors and these different systems.
5.
5. Additional amnesia models also seem to be alleviated by σ
1 ligands, such as phencyclidine-induced cognitive dysfunctions, and amnesia induced by the calcium channel blocker nimodipine, or by exposure to carbon monoxide. Furthermore, a preliminary study in an animal model of age-related memory deficits, the senescence-accelerated mouse, strengthened the therapeutic potentials of selective σ
1 receptor ligands in aging-related pathologies.