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Expression of parvalbumin and glutamic acid decarboxylase-67 after acute administration of MK-801. Implications for the NMDA hypofunction model of schizophrenia

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Abstract

Rationale

A reduction of GABAergic markers in postmortem tissue is consistently found in schizophrenia. This is generally mediated by a decreased expression of the calcium-binding protein, parvalbumin (PV), and the 67-kDa isoform of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD67). Similar reductions of PV or GAD67 are observed after repeated exposure to N-methyl-D-aspartate (NMDA) receptor antagonists but less attention has been paid to what occurs after their acute administration.

Objectives

Here, we have used in situ hybridization to examine the expression of PV and GAD67 mRNAs at 4 h and 24 h after an acute administration of MK-801 (1 mg/kg).

Results

Four hours after MK-801, the expression of PV mRNA decreased only in dentate gyrus of the hippocampus. Twenty four hours after this treatment, a reduction of the levels of PV mRNA was found in the medial prefrontal, orbitofrontal and entorhinal cortices, hippocampus and the basolateral nucleus of the amygdala. In contrast, no changes in the expression of GAD67 were observed in any of the brain regions examined. Interestingly, the reduction in PV mRNA expression is observed in discrete corticolimbic subregions that have been implicated in schizophrenia, which is coincident with changes observed in postmortem tissue of schizophrenia brain.

Conclusions

These findings indicate that acute administration of a NMDA antagonist delineate a pattern of changes in GABAergic markers different from those observed in postmortem tissue in schizophrenia inasmuch as only deficits in parvalbumin (but not GAD67) were seen.

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Acknowledgements

This work was supported by the Ministry of Health (FIS Grant PI070111 to A.A.), by the Ministry of Education and Science (SAF Grant 2006–10243 to G.M.), and by the Generalitat de Catalunya (SGR2009/220). All experiments adhered to the guidelines of the European Communities Council Directive of November 24, 1986 (86/609/EEC), and were approved by the Institutional Animal Care and Use Committee. The authors have nothing to disclose.

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Authors and Affiliations

  1. Department of Neurochemistry and Neuropharmacology, Instituto de Investigaciones Biomédicas de Barcelona, CSIC (IDIBAPS), Carrer Rosselló 161, 6th floor, room 630, 08036, Barcelona, Spain

    Tamara Romón, Guadalupe Mengod & Albert Adell

  2. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) www.cibersam.es

    Tamara Romón & Albert Adell

  3. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) www.ciberned.es

    Guadalupe Mengod

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  1. Tamara Romón
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  2. Guadalupe Mengod
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  3. Albert Adell
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Correspondence to Albert Adell.

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This work was supported by grants from the Ministry of Health, Ministry of Education and Science and the Generalitat de Catalunya.

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Romón, T., Mengod, G. & Adell, A. Expression of parvalbumin and glutamic acid decarboxylase-67 after acute administration of MK-801. Implications for the NMDA hypofunction model of schizophrenia. Psychopharmacology 217, 231–238 (2011). https://doi.org/10.1007/s00213-011-2268-6

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