Gender difference in the prevention of hyperanxiety in adult prenatally stressed rats by chronic treatment with amitriptyline

Objective: The study determined whether oral administration of amitriptyline for 6 weeks from before puberty to prenatally stressed (PS) male and female rats could prevent hyperanxiety in adulthood. Methods: Sprague-Dawley (12) rat dams were stressed by restraint in cylinders thrice daily for 45 min during the last week of pregnancy. Their offspring and those from unstressed dams (12) were given amitriptyline (4.5 mg/kg per day) in the drinking water between 4 and 10 weeks of age. Behaviour was assessed in the elevated plus maze (EPM) in week 10 in group 1 while still receiving the drug; in group 2, 2 weeks after stopping the drug, and in group 3, as in group 2, but after prior exposure to an open field (OF). Results: When tested while receiving the drug, no clear anxiolytic effect was seen in PS rats, and anxiety was actually increased in control rats, as indicated by the greater amount of time in closed arms of the EPM. Significant anxiolytic effects of amitriptyline (increase in time in open arms of EPM) were seen 2 weeks after stopping the drug in PS females. It could only be demonstrated in PS males after their anxiety in the EPM had been increased as a result of prior exposure to the open field. Conclusions: Chronic early treatment with amitriptyline can prevent the development of hyperanxiety in PS rats in adulthood. This effect is only detectable after cessation of drug treatment. The anxiolytic effect is more readily detected in females.