Chronic fluoxetine in tests of anxiety in rat lines selectively bred for differential 5-HT1A receptor function

Selective breeding for high and low sensitivity to the hypothermic response induced by the 5-HT1A receptor agonist 8-OH-DPAT has established two lines of rat (HDS and LDS, respectively) whose behavior differs in a model of de pression and in the social interaction test of anxiety. The HDS line has a higher level of anxiety and, furthermore, does not display the usual anxiog enic response to intrahippocampal administration of 8-OH-DPAT. It was there fore hypothesized that this line of rat might be a useful model of high tra it anxiety with a susceptibility to depression. We thus investigated whethe r chronic treatment with fluoxetine would result in an anxiolytic effect in the social interaction test in the LDS and HDS lines of rat. In both lines , acute fluoxetine (10 mg/kg) produced an anxiogenic effect in the social i nteraction test; when rats were tested 24 h after 14 days of fluoxetine tre atment there were no anxiolytic effects in either line. In the social inter action test, chronic fluoxetine treatment did not change either the anxioge nic effect of 8-OH-DPAT (100 ng) injected bilaterally into the dorsal hippo campus in the LDS line or the lack of response in the I-IDS line. In the el evated plus-maze, chronic fluoxetine treatment resulted in a significant an xiogenic effect in the HDS line, but was without effect in the LDS line. In trahippocampal 8-OH-DPAT was without effect in the plus-maze in either line . These results suggest that chronic treatment with fluoxetine did not modi fy the hippocampal 5-HT1A receptor in either line. The anxiogenic effects o bserved in the plus-maze in the HDS line after chronic fluoxetine might rel ate to line differences in 5-HT1A receptors in other brain regions. (C) 199 9 Elsevier Science Inc.