Poster 22: Schizophrenia is a debilitating psychiatric disorder characterized, in part, by severe cognitive impairments. These impairments greatly impede a schizophrenic patient's ability to function in society, and are not well-treated by current medications. One such cognitive impairment is cognitive inflexibility: the inability to adapt ones cognitive/behavioral responses to changing environments or task requirements. We used a maze-based task measuring rat cognitive flexibility to test whether a novel drug, TCS1205, a selective agonist of GABAA A receptors containing α2 subunits, could block cognitive flexibility deficits induced by the NMDA receptor antagonist MK-801. TCS1205 was injected into the prefrontal cortex before rats were tested on a cognitive shift paradigm. We found that TCS1205 administration blocks the impairing effects of MK-801 in a dose-dependent manner, while having no effect when administered alone. Our data support the hypothesis that deficiencies in inhibitory neurotransmission within the prefrontal cortex contribute to schizophrenia-associated cognitive problems.
