Repeated risperidone treatment increases the expression of NCAM and PSA-NCAM protein in the rat medial prefrontal cortex

The present study investigates whether the anti-schizophrenic drug risperidone may evoke changes in the expression of NCAM/PSA-NCAM proteins, an indispensable element in the remodeling of synaptic arrangements, in the medial prefrontal cortex (mPFC). Rats were treated with risperidone (0.2 mg/kg, i.p.) either once or repeatedly (once a day, for 21 days). The expression of NCAM and PSA-NCAM proteins was analyzed via western blot and immunohistochemistry at intervals of 3 h and 3, 6, and 9 days after the single or the last risperidone dose. Repeated (but not acute) administration of risperidone was found to increase the expression of NCAM-180, NCAM-140 and PSA-NCAM proteins at 3 or 6 days after treatment. PSA-NCAM immunoreactivity was found in cell bodies, perisomatic-like sites, and in the neuropil of the mPFC. Neither single nor repeated risperidone administration changed the number of PSA-NCAM neurons in the mPFC. In contrast, the repeated risperidone treatment increased the number of PSA-NCAM perisomatic-like sites and the length density of PSA-NCAM positive neuropil at 3 days after the last injection. The data obtained indicate that risperidone, given repeatedly, may promote the remodeling of the structure of presumably GABAergic interneurons and that it may evoke the rearrangement of the synaptic contact in the mPFC. (C) 2008 Elsevier B.V. and ECNP. All rights reserved.