Clozapine impact on c-Fos expression in mild stress preconditioned male rats exposed to a novelty stressor.

Clozapine (CLZ) stimulates several brain areas some of them being sensitive to stress. Aim of the present study was to reveal whether 7-day CLZ administration may: (1) activate the selected forebrain areas; (2) modulate response of these structures to a single forced swimming episode (FSW); (3) modulate response of these structures to FSW after 13-day preconditioning with mild unpredictable stress complex (CMS). Used groups of male Wistar rats: (a) vehicle or CLZ treated for 7 days; (b) vehicle or CLZ treated for 7 days and on the 7th day exposed to FSW; (c) CMS exposed for 13 days, from the 8th day injected with vehicle or CLZ and on the 14th day exposed to FSW. Vehicle or CLZ (10 mg kg  day in 0.1% acetic acid) were administered intraperitoneally. c-Fos quantification was performed 90 min after FSW in the medial prefrontal cortex (mPFC), dorsolateral (dLS) and ventrolateral (vLS) septum, dorsolateral (DLStr) and dorsomedial (DMStr) striatum, nucleus accumbens shell (NAc shell) and core (NAc core), and hypothalamic paraventricular nucleus (PVN). In unstressed animals CLZ increased c-Fos expression in the mPFC, vLS, and PVN. After a single FSW, CLZ decreased the number of c-Fos immunoreactive cells in the vLS, DMStr, NAc shell, and NAc core. In CMS rats, CLZ suppressed c-Fos immunoreactivity in response to FSW in the PVN. Our data indicate that CLZ elicits different impact on neuronal activities in the brain areas studied and modifies the response of these structures to stress. CLZ effect seems to be affected by stress duration.