Phencyclidine impairs latent learning in mice: Interaction between glutamatergic systems and sigma1 receptors

Akihiro Noda, Yukihiro Noda, Hiroyuki Kamei, Kenji Ichihara, Takayoshi Mamiya, Taku Nagai, Shin ichi Sugiura, Hiroshi Furukawa, Toshitaka Nabeshima

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Abstract

The effect of phencyclidine (PCP) on latent learning was investigated using a one-trial water-finding task in mice. Mice without water deprivation were given PCP or saline before a training trial, which consisted of exposure to a novel open-field environment with an alcove containing a water tube. Twenty to twenty-four hours after water deprivation, animals were placed in the same apparatus and the time required to find the water tube measured (test trial). Saline-treated trained mice showed a significantly shorter time to find the water tube during the test trial (finding latency) than naive mice that had not been trained. When PCP (1 mg/kg i.p.) was administered before the training trial, the finding latency was significantly prolonged in comparison with that in the saline-treated mice, indicating that PCP induced impairment of latent learning. 1-(3,4-Dimethoxy-phenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503: 0.3 mg/kg s.c.) and (+)-pentazocine (1 mg/kg s.c.), selective sigma1 receptor agonists, or D-cycloserine (10 and 30 mg/kg, s.c.), a glycine binding site agonist, significantly counteracted the PCP-induced impairment of latent learning, whereas (+)-SKF-10,047 (0.1-3 mg/kg s.c.), a putative sigma1 receptor agonist, did not. The ameliorating effects of SA4503 and (+)-pentazocine were antagonized by N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy) phenyl) ethylamine (NE-100: 1 mg/kg i.p.), a selective sigma1 receptor antagonist. SA4503 also ameliorated the impairment of latent learning induced by dizocilpine, a non-competitive N-methyl-D-aspartate receptor antagonist, the effect being antagonized by NE-100. These results suggest that PCP induces an impairment of latent learning, this effect being mediated via glutamatergic systems, and that activation of sigma1 receptors ameliorates impairment of latent learning induced by PCP.

Original languageEnglish
Pages (from-to)451-460
Number of pages10
JournalNeuropsychopharmacology
Volume24
Issue number4
DOIs
Publication statusPublished - 27-02-2001
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

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