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Repeated low dose of phencyclidine administration impairs spatial learning in mice: blockade by clozapine but not by haloperidol.
Eur Neuropsychopharmacol. 2008 Jul; 18(7):486-97.EN

Abstract

The effect of phencyclidine (PCP), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, was examined in the water maze, a spatial learning and memory task dependent on hippocampal functions. Male adult C57Bl/6J mice received daily (s.c.) injections of either saline or PCP (0.25-4.0 mg/kg) for 12 days. During the last 5 days, the injections were followed by water maze training. Repeated PCP treatments disrupted spatial learning and memory in the 0.5-4.0 mg/kg dose range. Severe sensorimotor disturbances, observed at the 2.0 and 4.0 mg/kg doses of PCP, precluded further swim maze testing. The 0.5 mg/kg but not the 1.0 mg/kg dose of PCP impaired spatial learning and memory without any apparent sensorimotor deficits. PCP, at 1.0 mg/kg, produced impairment in non-spatial learning in the swim maze task and motor disturbances in the rotarod test. Repeated daily treatment with either the "atypical" antipsychotic drug clozapine (0.5 mg/kg i.p.) or the "typical" antipsychotic drug haloperidol (0.05 mg/kg i.p.) failed to influence spatial performances. The spatial impairment caused by the 0.5 mg/kg dose of PCP was blocked by concomitant treatment with clozapine (0.5 mg/kg), but not with haloperidol (0.05 mg/kg). The results suggest that it is possible, at low doses of PCP, to dissociate the spatial learning impairment in the water maze from the adverse behavioral effects of NMDA receptor blockade. This model may provide a basis for the analysis of the mechanisms underlying declarative memory disturbances in schizophrenia and the differences in mechanisms between typical and atypical antipsychotic drugs.

Authors+Show Affiliations

Department of Neuroscience, Division of Behavioral Neuroscience, Retziusvag 8, B3:5, Karolinska Institutet, SE-171 77 Stockholm, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18242064

Citation

Beraki, Simret, et al. "Repeated Low Dose of Phencyclidine Administration Impairs Spatial Learning in Mice: Blockade By Clozapine but Not By Haloperidol." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 18, no. 7, 2008, pp. 486-97.
Beraki S, Kuzmin A, Tai F, et al. Repeated low dose of phencyclidine administration impairs spatial learning in mice: blockade by clozapine but not by haloperidol. Eur Neuropsychopharmacol. 2008;18(7):486-97.
Beraki, S., Kuzmin, A., Tai, F., & Ogren, S. O. (2008). Repeated low dose of phencyclidine administration impairs spatial learning in mice: blockade by clozapine but not by haloperidol. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 18(7), 486-97. https://doi.org/10.1016/j.euroneuro.2007.12.001
Beraki S, et al. Repeated Low Dose of Phencyclidine Administration Impairs Spatial Learning in Mice: Blockade By Clozapine but Not By Haloperidol. Eur Neuropsychopharmacol. 2008;18(7):486-97. PubMed PMID: 18242064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repeated low dose of phencyclidine administration impairs spatial learning in mice: blockade by clozapine but not by haloperidol. AU - Beraki,Simret, AU - Kuzmin,Alexander, AU - Tai,Fadao, AU - Ogren,Sven Ove, Y1 - 2008/01/31/ PY - 2007/07/18/received PY - 2007/10/26/revised PY - 2007/12/12/accepted PY - 2008/2/5/pubmed PY - 2008/9/25/medline PY - 2008/2/5/entrez SP - 486 EP - 97 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 18 IS - 7 N2 - The effect of phencyclidine (PCP), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, was examined in the water maze, a spatial learning and memory task dependent on hippocampal functions. Male adult C57Bl/6J mice received daily (s.c.) injections of either saline or PCP (0.25-4.0 mg/kg) for 12 days. During the last 5 days, the injections were followed by water maze training. Repeated PCP treatments disrupted spatial learning and memory in the 0.5-4.0 mg/kg dose range. Severe sensorimotor disturbances, observed at the 2.0 and 4.0 mg/kg doses of PCP, precluded further swim maze testing. The 0.5 mg/kg but not the 1.0 mg/kg dose of PCP impaired spatial learning and memory without any apparent sensorimotor deficits. PCP, at 1.0 mg/kg, produced impairment in non-spatial learning in the swim maze task and motor disturbances in the rotarod test. Repeated daily treatment with either the "atypical" antipsychotic drug clozapine (0.5 mg/kg i.p.) or the "typical" antipsychotic drug haloperidol (0.05 mg/kg i.p.) failed to influence spatial performances. The spatial impairment caused by the 0.5 mg/kg dose of PCP was blocked by concomitant treatment with clozapine (0.5 mg/kg), but not with haloperidol (0.05 mg/kg). The results suggest that it is possible, at low doses of PCP, to dissociate the spatial learning impairment in the water maze from the adverse behavioral effects of NMDA receptor blockade. This model may provide a basis for the analysis of the mechanisms underlying declarative memory disturbances in schizophrenia and the differences in mechanisms between typical and atypical antipsychotic drugs. SN - 0924-977X UR - https://www.unboundmedicine.com/medline/citation/18242064/Repeated_low_dose_of_phencyclidine_administration_impairs_spatial_learning_in_mice:_blockade_by_clozapine_but_not_by_haloperidol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-977X(07)00246-5 DB - PRIME DP - Unbound Medicine ER -