Social withdrawal is one of the negative symptoms of schizophrenia, which often precedes the onset of the first psychotic episode and persists for most of patient‘s life. Current antipsychotics are relatively ineffective in normalize this social dysfunction. There are only a few studies addressing the efficacy of antipsychotic drugs in animal models of social deficits. The aim of the present study was to evaluate the effects of the selective serotonin 5HT2A, 5HT6 and 5HT7 receptor antagonists in ketamine-induced schizophrenia-like social deficit in rats. After 5 days of social isolation male Sprague-Dawley rats were individually adapted to the open field arena for 7 minutes. On the next day, two unfamiliar rats of matched body weight received the same treatment and were placed in the open field arena for 10 minutes. The active, non-agressive social behaviors were scored: sniffing, social grooming , following, mounting and climbing. Ketamine caused significant reduction of the time of active social behavior. Administration of 5HT7 but not 5HT6 or 5HT2A receptor antagonist reversed ketamine-induced social deficits. Present findings suggest the importance of 5HT7 receptor antagonism in ameliorating the negative symptoms of psychoses. It is noteworthy that most recently synthesized second and third generation antipsychotic exhibit a high, nano-molar affinity for 5HT7 receptor. Supported by the Statutory Funds of the Institute of Pharmacology, Polish Academy of Sciences.
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