Pharmacopsychiatry 2005; 38 - A021
DOI: 10.1055/s-2005-918643

Ultrastructural alterations of GABAergic interneurons in an animal model of psychosis

I Braun 1, JJK Genius 1, N Kastrup 1, AM Hartmann 1, I Giegling 1, HJ Möller 1, D Rujescu 1
  • 1Klinik für Psychiatrie und Psychotherapie, Ludwig Maximilians Universität München

Objectives:

Several studies reported alterations in distinct subgroups of inhibitory GABAergic interneurons (IN) within the prefrontal cortex (PFC) and hippocampal formation (HC) in schizophrenic patients. These IN exert important control over the excitatory function of pyramidal cells. Due to the fact, that IR express distinct types of calcium binding proteins (CBP), like parvalbumin (PV), calretinin (CR) and calbindin (CB), we were able to differentiate these cells in an rat model based on chronic NMDA-antagonism with MK–801 at subanesthetic doses. We hypothesized that a reduction of PV+ IN may lead to abnormal cognitive function.

Methods:

48 adolescent rats received MK–801 (0.02mg/kg), haloperidol (1mg/kg), combination of both drugs or saline for 21 days. The animals underwent extensive behaviour tests. One hippocampus was processed for gene expression analysis (Affymetrix rat genome 230 2.0 microarray), the other hemisphere was stained immunohistochemically for PV, CR and CB.

Results:

MK–801 exposure led to an – albeit subtle- alteration of the HC and PFC cytoarchitecture and regional distribution of CBPs as well as to changes of behavioural performance and neurological function.

Conclusions:

In good agreement with previous data we could demonstrate distinct alterations of CBP-containing IN, especially PV+ IN in the HC and PFC. These findings may account for some of the behavorial abnormalities exhibited by MK–801 treated rats.