Effects of Decreasing Cortical GABA Function on Social Behavior in Rats

Science Center, Bent Corridor

Negative symptoms of schizophrenia significantly decrease quality of life of those who suffer from this disorder. The underlying mechanisms of these symptoms are poorly understood. Our research focused on determining whether the inhibitory neurotransmitter GABA contributes to the expression of negative symptoms. It is widely known that individuals with schizophrenia have cortical GABA function abnormalities. We hypothesized that these abnormalities in GABA function contributed to negative symptoms of schizophrenia. To model the changes in GABA function we infused one of two drugs, Bicuculline (BMI) or L-allylglycine (LAG), into prefrontal cortex of rats. BMI is a GABAA receptor antagonist and LAG is a GABA synthesis inhibitor; both manipulations decrease GABA function. After rats were infused with a drug they were tested on two tests of social behavior (the social preference test and the social interaction test) and one test of reward (sucrose intake test). Asociality and anhedonia are common negative symptoms of schizophrenia. In the social preference test, increased doses of BMI decreased the time that the experimental rat interacted with a confined stimulus rat, however no effect was seen for increasing doses of LAG. In the social interaction test, the same pattern was revealed: increasing doses of BMI corresponded to lower social interaction times, while LAG had no noticeable effect. All groups of rats, including controls, significantly preferred drinking 10% sucrose solution to water, allowing us to conclude that neither of the drugs induced anhedonia symptoms in the rats. Our data suggests that GABAA receptor dysfunction plays a major role in the onset of negative symptoms, while GABA synthesis dysfunction may not contribute to the onset of these behaviors. Future work will investigate they subtypes of GABAA receptors that may contribute to the negative symptoms of schizophrenia.