Effect of a neuroactive steroid infused into the cerebral ventricles of fetal sheep in utero using small infusion volumes

Placental progesterone metabolites may influence fetal behaviour during lat e gestation. We have investigated the effect of the neuroactive metabolite, pregnanolone, on the sleep/awake behaviour of fetal sheep. These studies c an only be effectively performed in unanesthetized animals with chronically implanted leads and catheters. The relatively large internal volumes of th ese catheters raises problems for cerebroventriclear infusions. Therefore, we developed a device with negligible deadspace (approximate to 10 mu l) co nsisting of a ventricular cannula attached to a small cap which allowed the instillation of yl volumes of neuroactive steroids into a cerebral ventric le of fetal sheep in utero. Two catheters attached to the cap allow it to b e filled in a push-pull configuration. The smaller internal diameter of the ventricular cannular prevents the solution entering the ventricle until th e outflow catheter is occluded and solution is forced through the probe. Us ing this device, the infusion of 5 beta-pregnane-3 alpha-ol-20-one (pregnan olone, 1 mg), in 35% hydroxypropyl-beta-cyclodextrin, resulted in a marked suppression of fetal behaviour parameters indicative of arousal, while vehi cle alone did not affect these parameters. We conclude that neuroactive ste roids can be infused into the cerebroventricular system of chronically cath eterised fetal sheep in small volumes and that pregnanolone may act directl y to influence fetal behaviour. (C) 2000 Elsevier Science B.V. All rights r eserved.