XEN1101 is a differentiated Kv7 potassium channel modulator being developed for the treatment of epilepsy. Kv7 channels have recently been implicated in depression and anhedonia, both of which are relatively common co-morbidities of epilepsy. An assessment of XEN1101 in acute rodent models of depression and anhedonia was undertaken. The forced swim test (FST) is a model of behavioral despair, and is sensitive to various classes of antidepressant drugs. Mice received a single dose of 1 mg/kg or 3 mg/kg XEN1101, 30 mg/kg imipramine, or vehicle. Thirty minutes post-dose, animals were placed into glass cylinders filled with water. After a period of vigorous activity, mice stop swimming and adopt an immobile posture. Over a 6-minute test session, the 1 mg/kg and 3 mg/kg XEN1101 dose groups showed a dose-dependent trend towards increased latency to immobility as well as a dose-dependent reduction in time spent immobile (154 ± 49.9 seconds and 142 ± 42.8 seconds for 1 and 3 mg/kg doses, respectively, compared to 201 ± 42.9 seconds for vehicle (p<0.05)); both indicative of an anti-depressant effect. The progressive ratio test (PRT) is a model of anhedonia. The effect of XEN1101 on the motivation of trained rats to respond with a lever press for a food reward was assessed. The rats followed a progressive schedule of reinforcement in which the number of lever presses required to obtain a food reward increased for successive reinforcers. The break point was defined as the point at which a rat failed to earn a food pellet in 20 minutes. The number of food pellets earned was the primary measure of efficacy, with increases indicating improvements in anhedonia. In a cross-over design, rats received a single dose of 1, 3, or 8 mg/kg XEN1101, 0.6 mg/kg amphetamine (as a positive control), or vehicle. XEN1101 significantly increased the number of food pellets earned at the break point for both the 3 mg/kg (n=12.5 ± 0.4) and 8 mg/kg doses (n=12.8 ±0.5), respectively, compared to n=11.5 ± 0.5 for vehicle (p<0.05 and p<0.01, respectively)). The results from these two studies support a potential benefit of XEN1101 in mood disorders.