ISSN:
1435-1463
Keywords:
Sigma sites
;
PRE-084
;
nimodipine
;
calcium channels
;
passive avoidance
;
alternation behaviour
;
water-maze
;
amnesia
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The high selectivity of the phencyclidine derivative PRE-084 for sigma (σ) sites is demonstrated. We previously reported that this compound is able to markedly attenuate the impairment of learning induced in mice by the non-competitive NMDA antagonist MK-801, and the cholinergic nicotinic antagonist mecamylamine. In this study, we examined the effect of PRE-084 on the impairment of learning induced by acute administration of the calcium channel antagonist nimodipine. Nimodipine (0.3mg/kg i.p.) impaired the spontaneous alternation behaviour in a Y-maze, decreased the step-down latency (SDL) in a passive avoidance task, and altered place learning and retention in a water-maze paradigm, with no marked effect on the motility observed using an open-field test. Preadministration of PRE-084 resulted in an attenuation of the impairment of alternation, in the 0.3–1 mg/kg s.c. range, in a marked increase in SDL, at 1–3 mg/kg, and improved place learning and retention in the water-maze, at 1 mg/kg. The effects on alternation behaviour and passive avoidance were completely prevented by co-administration of the purported σ antagonist BMY-14802 (10 mg/kg i.p.), implicating the σ sites. These results confirm the beneficial effect of the σ ligand PRE-084 on pharmacological models of learning impairments, and indicate that σ sites may modulate Ca2+ fluxes through VDCC, which may in turn bear some as yet unknown relationship to the previously described interaction with neurotransmitter systems.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01276561
Permalink
