Our previous studies showed the modulation of cocaine and amphetamine regulated transcript (CART) positive neurons and CART mRNA by adrenalectomy and corticosterone replacement in hypothalamic nuclei of male rat brain. More recently, we have shown by CART immunohistochemistry that restraint and forced swim (FS) stress have sexually dimorphic and regionally specific effects on CART expression in the hypothalamic nuclei of male and female Sprague-Dawley rats. This study aimed to evaluate the effects of FS stress on CART peptide expression in hypothalamus, amygdala and hippocampus of male and female (in or near estrus) Sprague-Dawley rats. Initially basal CART levels in regions of interest were determined in male and female rats; no sex differences were observed. In FS test, rats were forced to swim on two consecutive days, in a Plexiglas cylinder for 15 and 6 min, respectively. Rats were decapitated on the second day, 10 min after the stress procedure. Hypothalami, amygdalae and hippocampi were dissected and homogenized. CART peptide expression in these regions was measured by Western blotting. In males, FS increased CART expression in hypothalamus and amygdala. On the other hand, in females, FS lowered CART expression in amygdala. CART expression in hippocampus was not affected by the stress procedure in either sex. Our results suggest sexually dimorphic modulation of CART expression in hypothalamus and amygdala by FS procedure. Although modulation of the CART peptide by glucocorticoids and gonadal hormones appears likely, future studies are needed to elucidate the underlying mechanisms in the involvement of CART peptide in stress response. (c) 2006 Elsevier Ltd. All rights reserved.