Anxiolytic effects of the neuroactive steroid pregnanolone (3 alpha-OH-5 beta-pregnan-20-one) after microinjection in the dorsal hippocampus and lateral septum

The anxiolytic effects of the neuroactive steroid, 3 alpha-OH-5 beta-pregna n-20-one (pregnanolone), were determined after injection into the dorsal hi ppocampus or lateral septum in adult male rats. An increase in the proporti on of time spent on the open arms of the elevated plus-maze was found after 2.5 and 5 mu g of pregnanolone in the hippocampus, but not in the lateral septum. Intrahippocampal injection of 2.5 mu g of the 3 beta-epimer of preg nanolone did not affect behavior in the plus-maze; a higher dose of 5 mu g produced an anxiogenic effect. In the shock-probe burying test latency to b urying behavior was increased by intrahippocampal or intraseptal injection of 2.5 and 5 mu g of pregnanolone; the duration of burying behavior was dec reased by 0.5, 2.5 and 5 mu g of pregnanolone injection in the dorsal hippo campus or lateral septum. The number of contacts with the shock probe was n ot affected by any dose of pregnanolone in either intracranial site of inje ction. The anxiolytic effects of intrahippocampal or intraseptal injection of pregnanolone were blocked by intracranial pretreatment with 20 ng of pic rotoxin, but not by microinjection of 5 mu g of flumazenil or 200 ng of PK 11195. Thus, inhibition of the hippocampus, mediated by the pregnanolone's action at the GABA(A) receptor, produces a general anxiolytic effect. Howev er, similar inhibition in the lateral septum attenuates active avoidance of anxiogenic stimuli (i.e., decreased burying behavior), but not passive avo idance of aversive stimuli (i.e., exploration of open arms of the plus-maze and number of shocks in the probe burying test). (C) 1999 Elsevier Science B.V. All rights reserved.