Figure 6.

p11 is required for the behavioral antidepressant actions of a selective 5-HTR4 partial agonist (RS67333). p11 knock-outs and wild-type littermate controls were injected with RS67333 or saline vehicle for 3–5 d before behavioral testing. Immobility is an index of antidepressant activity in both the TST and FST. a, c, Consistent with the action of an antidepressant, RS67333 reduced time spent immobile in the TST (a) and FST (c) in wild-type mice but had no effect in p11 knock-out mice. In the TST (a) EMDT, an agonist for 5-HTR6 (a 5-HT receptor that does not interact with p11) reduced immobility in both p11 KO and WT mice. b, Treatment of WT mice with GR125487, a 5-HTR4 antagonist, blocked the antidepressant-like effect of RS67333 in the TST. d, RS67333 had an anxiolytic effect in the Open Field, reducing thigmotaxis in wild-type mice, but not in p11 knock-out mice. All data are presented as means ± SEM *p < 0.05, **p < 0.01