Effects of reboxetine and citalopram pretreatment on changes in cocaine and amphetamine regulated transcript (CART) expression in rat brain induced by the forced swimming test.

Cocaine and amphetamine regulated transcript (CART) has been implicated in the regulation of the stress response. Although the forced swimming test (FST), in which rats are forced to swim for 15 min (pretest swim) and then again for 5 min (test swim) 24 h later, has been used to study the effects of antidepressants, there have been few studies examining the effects of antidepressants on FST-induced changes in CART mRNA levels in the brain. To answer this question, we injected reboxetine and citalopram into male Sprague-Dawley rats 1, 5, and 23.5 h before the test swim and then sacrificed rats 2 h after the test swim, at the peak of the FST-induced increase in CART expression. The FST significantly increased CART mRNA levels in the nucleus accumbens, central nucleus of the amygdala, and locus ceruleus 2 h after the test session. Both reboxetine and citalopram pretreatment blocked FST-induced increases in CART mRNA levels in the nucleus accumbens, central nucleus of the amygdala, and locus ceruleus, despite the fact these antidepressants exert their therapeutic effect by different mechanisms. In addition, the FST significantly increased plasma corticosterone levels, and this effect was also blocked by reboxetine and citalopram pretreatment. These results suggest that inhibition of FST-induced increases in CART expression in the nucleus accumbens, central nucleus of the amygdala, and locus ceruleus may be a common mechanism of antidepressant effects during the FST.