1. Sigma (
sigma) receptor ligands were previously reported to alleviate learning and memory impairments on several pharmacological and pathological rodent models of
amnesia. Such effect was demonstrated as involving the sigma1 subtype of
sigma receptor. 2. In this study, we characterized the pharmacological effect mediated by sigma
ligands on two lesional models of
amnesia in mice: (1) the
hypoxia-related learning and memory impairment model induced by repeated exposure to
carbon monoxide (CO) gas; and (2) the intoxication with
trimethyltin (1 mg kg(-1)). 3. The selective sigma1
ligand PRE-084 (1 mg kg(-1)) or the non-selective sigma1/sigma2 compounds DTG (0.1 mg kg(-1)),
BD1008 (3 mg kg(-1)), and
haloperidol (0.1 mg kg(-1)) reversed significantly the spontaneous alternation deficits observed 7 days after exposure to CO or 14 days after intoxication with
trimethyltin. 4. The selective sigma1 receptor antagonist
NE-100 (1 mg kg(-1)) was ineffective by itself, but blocked completely the
PRE-084 effects, partially the DTG effects, and did not affect the effects induced by
BD1008 or
haloperidol. 5. A similar pharmacological profile was observed in the step-down type passive avoidance test performed 8 days after exposure to CO. 6. These results show that, in contrast to the previously reported
amnesia models, the impairments induced after exposure to CO or intoxication with
trimethyltin could be alleviated not only by sigma1 receptor agonists but also by sigma2 agonists. The particular pattern of neurodegeneration observed in these lesional models may explain these differences.