Figure 6.

Rcan1 KO mice are resistant to the acute anxiogenic effects of SSRI administration. A, WT but not Rcan1 KO mice injected with intraperitoneal fluoxetine and tested 24 h later in the EPM show decreased open-arm time compared with their vehicle-treated (WT or KO) cohorts, indicating increased anxiety in fluoxetine-treated WT mice. B, Fluoxetine treatment does not change overall locomotor activity within or across genotypes. Total distance traveled for test period is shown. C, Open-arm time of EPM-naive mice following either 3 or 15 d of treatment with fluoxetine or vehicle. All animals tested had no prior experience with the EPM. Fluoxetine-treated Rcan1 KO mice increase time spent in the open arms, indicating reduced anxiety, compared with vehicle-treated KO mice after 3 d of treatment. After 15 d of treatment, fluoxetine-treated WT mice show a significant increase in open-arm time compared with WT-vehicle controls on day 3 or 15. Fluoxetine treatment also increased open-arm time in Rcan1 KO mice on day 15 compared with vehicle treatment, but the difference did not reach statistical significance. D, Total distance moved in the EPM by all the treatment groups is similar. No difference in movement was observed in EPM-naive animals tested after 1, 3, or 15 d of treatment. N (day 1, day 3, day 15) = (11, 9, 9) KO-vehicle; (12, 7, 8) WT-vehicle; (10, 9, 9) KO-fluoxetine; (11, 6, 6) WT-fluoxetine. WT-fluoxetine day 3 vs WT-day 15 fluoxetine denoted by *p < 0.05; **p < 0.01; *** or ‡p < 0.001; n.s., p > 0.05.