PRE-084, a σ selective PCP derivative, attenuates MK-801-induced impairment of learning in mice

Tangui Maurice, Tsung Ping Su, Daniel W. Parish, Toshitaka Nabeshima, Alain Privat

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Abstract

We investigated the effect of the σ selective PCP derivative PRE-084 on the impairment of learning induced in mice by the noncompetitive NMDA antagonist MK-801. Learning capacities were evaluated using the spontaneous alternation in a Y-maze test for spatial working memory, the step-down passive avoidance and the elevated plus-maze test for long-term memory. At doses about 1 mg/kg IP, PRE-084 significantly attenuated MK-801 (0.2 mg/kg IP) induced impairment of learning. The dose-response curve was bell-shaped which is typical for cognition enhancers. The effect of PRE-084 was antagonized by BMY-14802 (10 mg/kg IP) and suppressed by a chronic treatment with haloperidol (4 mg/kg/day SC for 7 days). Furthermore, PRE-084 did not affect scopolamine (1 mg/kg SC) induced amnesia but significantly attenuated mecamylamine (10 mg/kg IP) induced amnesia. These results show that σ sites mediate a modulation of the NMDA receptor complex-dependent learning processes and may similarly affect the cholinergic nicotinic memory processes. Moreover, the PCP derivative PRE-084, acting selectively at σ sites, reverses the amnesia induced by a drug acting at the PCP site.

Original languageEnglish
Pages (from-to)859-869
Number of pages11
JournalPharmacology, Biochemistry and Behavior
Volume49
Issue number4
DOIs
Publication statusPublished - 12-1994

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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