Relationship between increased binding potential of possible 5-HT2A receptors in the ventral hippocampus by subchronic phencyclidine and disturbed social interaction in rats: a PET study using 18F-altanserin.

Abstract

Subchronic administration of the psychotomimetic drug phencyclidine is known to exacerbate serotonin 5-HT2A receptor-relevant behavioral abnormalities. However, the effects of subchronic phencyclidine on 5-HT2A receptors remain unclear. Here, we investigated the effects of subchronic phencyclidine on the binding potential (BPND) of 5-HT2A receptors in the rat brain using positron emission tomography. Adult male Sprague-Dawley rats received intraperitoneal injection of either phencyclidine (10 mg/kg) or physiological saline once daily, a total of 15 times. positron emission tomography scans were performed twice, before and after drug administration, using 18F-altanserin, a selective 5-HT2A receptor radioactive marker. Two behavioral tests, the sociability test and the social interaction test, were performed before each positron emission tomography scan. The social interaction time was significantly shortened by subchronic phencyclidine. The BPND of the 5-HT2A receptors was significantly increased after subchronic phencyclidine administration in the medial prefrontal cortex, ventral hippocampus, motor cortex, and somatosensory cortex. The BPND change between the pre- and postdrug periods in the ventral hippocampus showed a significant negative correlation (r = 0.73) with that of the social interaction time change. Our results suggest that upregulation of 5-HT2A receptors in the ventral hippocampus may play a role in disturbed social ability and the development of negative symptoms.