Characterization of dopamine D2 receptor binding, expression and signaling in different brain regions of control and schizophrenia-model Wisket rats.

• Stimulation of D 2 R caused enhanced G-protein activation in several brain sites of Wisket animals. • Maximal binding capacity of D 2 Rs increased in the model animals. • D 2 R mRNA expression showed a trend for the increase in brain areas of Wisket animals. • D 2 R protein expression increased in the hippocampus and the PFC in Wisket rats. • Schizophrenia-like Wisket animals show altered D 2 receptor expression and function. In previous studies we have shown that a three-hit animal model of schizophrenia (Wisket rat) has several behavioral impairments related to the disorder along with altered mu-opioid (MOP) and cannabinoid (CB1) receptor signaling. As the dopamine hypothesis of schizophrenia is central to research in the field, the goal of the present study was to investigate dopaminergic D 2 receptor (D 2 R) functions (binding capacity, G-protein activation and expression) in several brain regions (hippocampus, prefrontal cortex, striatum, olfactory bulb, cerebellum, brainstem, cortex and diencephalon) of control (Wistar) and Wisket rats. It was found that the D 2 R mediated maximal activation of G-proteins was substantially higher in hippocampus, striatum and olfactory bulb membranes prepared from the Wisket than in control animals, which was accompanied with lower potency of the D 2 R-mediated G-protein activation. In contrast, enhanced potency was detected in the prefrontal cortex without changes in the maximal activation. In saturation binding assays the maximal binding capacity of D 2 Rs was higher in the model animals in cerebral cortex, striatum and lower in the brainstem, while no changes in the dissociation constant values were detected. The D 2 R mRNA expression showed a trend for greater level in the investigated areas, while the D 2 R protein expression was significantly higher of Wisket rats compared to Wistar animals in the hippocampus and in the prefrontal cortex but not in the cerebellum. This study proved that the Wisket animals show altered D 2 receptor expression and function which might be related to the schizophrenia-like symptoms. [ABSTRACT FROM AUTHOR]