Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the antibiotic drug minocycline

Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):336-9. doi: 10.1016/j.pnpbp.2007.08.031. Epub 2007 Aug 29.

Abstract

Background: The N-methyl-d-aspartate (NMDA) receptor antagonist phencyclidine (PCP)-induced cognitive deficits have been used as an animal model for schizophrenia. This study was undertaken to determine whether the antibiotic drug minocycline could improve PCP-induced cognitive deficits in mice.

Methods: Saline (10 ml/kg/day, s.c., once daily on day 1-5, 8-12) or PCP (10 mg/kg/day, s.c., once daily on day 1-5, 8-12) were administered to mice for 10 days. Subsequently, vehicle (10 ml/kg/day, i.p.) or minocycline (4.0 or 40 mg/kg/day, i.p.) was injected for 14 consecutive days. One day after the final injection, a novel object recognition test was performed.

Results: PCP-induced cognitive deficits in mice were significantly improved by subsequent subchronic (14 days) administration of minocycline (40 mg/kg), but not minocycline (4.0 mg/kg).

Conclusions: This study suggests that minocycline could be a potential therapeutic drug for cognitive deficits in schizophrenic patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Behavior, Animal / drug effects*
  • Cognition Disorders / chemically induced*
  • Cognition Disorders / drug therapy*
  • Drug Administration Schedule
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / adverse effects
  • Excitatory Amino Acid Antagonists / pharmacology
  • Exploratory Behavior / drug effects
  • Humans
  • Injections, Subcutaneous
  • Male
  • Mice
  • Mice, Inbred ICR
  • Minocycline / pharmacology
  • Minocycline / therapeutic use*
  • Phencyclidine / administration & dosage
  • Phencyclidine / adverse effects*
  • Phencyclidine / pharmacology
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Schizophrenia / drug therapy
  • Schizophrenic Psychology

Substances

  • Anti-Bacterial Agents
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Minocycline
  • Phencyclidine