Antidepressant effects of Spadin. A) Forced Smimming Test (FST), spadin-treated mice have a shorter time of immobility comparable to that obtained with TREK-1 KO or fluoxetine-treated mice, whatever the way of spadin administration: intracerebroventricular (i.c.v), intravenous (i.v) or intraperitoneal (i.p). Acute treatments: Spadin (10⁻⁴ to 10⁻⁸ M) or Fluoxetine (3 mg/kg) or Saline solutions are injected 30 min before the test in wild-type and TREK-1 KO mice. B) Novelty-Suppressed Feeding Test (NSF): Subchronic treatments: Spadin (10⁻⁶ M), Fluoxetine (1 mg/kg) or Saline solutions are i.v. injected in a 100 μL bolus once a day for 4 successive days before the test. In chronic treatments, spadin (10⁻⁶ M) and fluoxetine (1 mg/kg) are i.v. injected in a 100 μL bolus once a day for 21 successive days. At the end of the AD treatment, animals are food deprived for one day and then measured for their latency to feed. 4-day treatment with Spadin significantly reduces the latency to feed when compared to saline or fluoxetine treatments.