Altinicline

Sprague-Dawley (male, 200-240 g, learned helplessness model induced by inescapable footshocks)^[1]

0.375 mg/kg/day; 0.75 mg/kg/day; 1.5 mg/kg/day (subchronic); 1.5 mg/kg/day (chronic)

s.c.; subchronic: 5 consecutive days (single bolus on day 1, split doses days 2-5); chronic: 4 weeks daily bolus prior to testing, plus split doses days 2-5 post-testing start

Produced dose-dependent reversal of inescapable shock-induced escape failures at 1.5 mg/kg/day subchronic treatment: session 1 escape failures = 10, session 2 = 4, session 3 = 5, session 4 = 5 (all significantly different from vehicle controls, P<0.05).
Produced significant session-dependent increase in avoidance responding in inescapable shock rats at 1.5 mg/kg/day subchronic treatment, with statistically significant elevations in sessions 2, 3, and 4 compared to vehicle controls.
Produced no significant effect on intertrial crossings or shock sensitivity with subchronic treatment.
Significantly reversed escape failures in inescapable shock rats at 1.5 mg/kg/day chronic treatment: session 1 escape failures = 10, session 2 = 5, session 3 = 5, session 4 = 3 (all significantly different from vehicle controls, P<0.05).
Produced significant increase in avoidance responding at 1.5 mg/kg/day chronic treatment: session 4 = 10 responses, compared to 0 in vehicle controls.
Significantly increased intertrial crossings in sessions 2 and 4 compared to vehicle controls with 1.5 mg/kg/day chronic treatment.
Blocked escape failure reversal effect of subchronic 1.5 mg/kg/day treatment by co-administration of 6 mg/kg/day mecamylamine.
Retained antidepressant-like effects (escape failure reversal) for 1 week following cessation of drug administration.