Effect of chronic treatment with ladostigil (TV-3326) on anxiogenic and depressive-like behaviour and on activity of the hypothalamic-pituitary-adrenal axis in male and female prenatally stressed rats

Objective: The aim of the study is to investigate the effect of ladostigil, a cholinesterase and brain-selective Monoamine Oxidase (MAO) inhibitor, on anxiogenic and depressive-like behaviour and the response of the hypothalamic-pituitary-adrenal axis to stress in prenatally stressed (PS) male and female rats.

Methods: Ladostigil (17 mg/kg/day) was administered daily for 6 weeks to control and PS rats aged 6 weeks. Behaviour was assessed in the elevated plus maze (EPM) and forced swim tests (FST). Plasma corticosterone (COR) was measured before, 30 and 90 min after exposure to stress.

Results: Ladostigil inhibited brain MAO-A and B by more than 60%, significantly reduced hyperanxiety of male and female PS rats in the EPM and depressive-like behaviour in the FST without affecting that of controls and restored the delayed return to baseline of plasma COR in PS rats after exposure to stress to that of control rats.

Conclusions: A novel brain-selective MAO inhibitor, ladostigil can selectively reverse the behavioural and neurochemical effects induced by prenatal stress without affecting the behaviour of controls.