Behavioral evidence for a modulating role of σ ligands in memory processes. II. Reversion of carbon monoxide-induced amnesia

Tangui Maurice, Masayuki Hiramatsu, Tsutomu Kameyama, Takaaki Hasegawa, Toshitaka Nabeshima

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46 Citations (Scopus)


This study examined the effect of low doses of σ ligands amnesia induced in mice by successive carbon monoxide (CO) exposure. Mice were exposed three consecutive times to CO (10 ml/min, 30-50 s) at 38°C. Spatial working memory impairment was investigated 5 days later by monitoring spontaneous alternation behavior in a Y-maze. Delayed amnesia was examined 7 days after CO exposure by using a step-down passive avoidance test. The preadministration of the σ ligand 1,3-di-(2-tolyl)guanidine (DTG), at doses of 1 to 1000 μg/kg, s.c., 30 min before CO exposure did not affect the resulting amnesia in either test. However, when administered 30 min before the test, i.e., 5 or 7 dats after CO exposure, this agent completely reversed the CO-induced decrease in alternation performance, at doses of 10 to 100 μg/kg. The same effect was observed with (+)-N-allylnormetazocine ((+)-SKF 10,047), at doses of 100 to 300 μg/kg, but not with (-)-SKE 10,047. DTG, at the same dose range that reversed the decrease in alternation, also totally reversed the CO-induced decrease in step-down latency in the passive avoidance test. The curve for these effects was bell-shaped; the effects were not observed at the dose of 1 mg/kg. Moreover, α-(-4-fluorophenyl-2-pyrimidinyl)-1-piperazine butanol (BMY 14802), a putative σ antagonist (1-10 mg/kg i.p), did not affect CO-induced amnesia, but when simultaneously administered with DTG, it completely prevented its effect in both tests. These findings indicate that σ1 sites may mediate a complete but bell-shaped reversion of CO-induced amnesia. The exact mechanisms remain to be determined, but they may involve the modulation of both N-methyl-d-aspartate and cholinergic nicotinic systems.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalBrain Research
Issue number1
Publication statusPublished - 30-05-1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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