ANXYOLITIC EFFECTS OF THE NEUROSTEROID PREGNANOLONE: INFLUENCE OF GENDER AND HORMONAL BACKGROUND

YUNES R.; CASTELLER G.; ROBY L.; BUXTON N.; CABRERA R.

Mar del Plata

Congreso; XXXVII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2005

SAFE

Anxyolitic effects of the neurosteroid pregnanolone: influence of  gender and hormonal background. Yunes R1, Casteller G1,2, Roby L1, Buxton N2, Cabrera R1,2. 1-IMBECU (CONICET), Area de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, 5500 Mendoza ? Argentina  ryunes@fcm.uncu.edu.ar  2- Facultad de Ciencias de la Salud. Universidad de Mendoza. It has been reported that neurosteroids exposure may influence both the pharmacological properties of the GABAA receptor as well as the manifestation of anxiety in both sexes. To test this hypothesis this study compared the behavioral effects of pregnanolone regarding different hormonal status and gender. Adult Sprague-Dawley male rats, intact and castrated, and females at 15th day of pregnancy were used (n = 8 animal/group). Pregnanolone 6 µM and Krebs (KRB) solution were inyected by intraventricular brain injection. Anxiety (total arm spent exploring the open arm: TOA) and locomotion activity (number of total arm entries: TLA) were tested on an elevated plus-maze. Our results showed that TOA was significantly shorter in treated pregnant females (p < 0.05, Students t test). On the other hand, castrated males treated with testosterone did not show any change in their anxiety levels. However, when treated with estrogen the animals were clearly more anxious that their corresponding controls. Interestingly, pregnanolone was able of reverting this anxiolytic effect. From our results we conclude that: 1) progesterone was probably responsible of priming the pregnanolone effect in pregnant females; 2) the priming effect was sex-dependent since it was not present in males;  and 3) pregnanolone, in males, is clearly anxiolytic, probably by modulating GABAA receptors.