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

The anxiolytic effects of the neuroactive steroid, 3 alpha-OH-5 beta-pregnan-20-one (pregnanolone), were determined after injection into the dorsal hippocampus or lateral septum in adult male rats. An increase in the proportion 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 pregnanolone 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 burying behavior was increased by intrahippocampal or intraseptal injection of 2.5 and 5 mu g of pregnanolone; the duration of burying behavior was decreased by 0.5, 2.5 and 5 mu g of pregnanolone injection in the dorsal hippocampus or lateral septum. The number of contacts with the shock probe was not affected by any dose of pregnanolone in either intracranial site of injection. The anxiolytic effects of intrahippocampal or intraseptal injection of pregnanolone were blocked by intracranial pretreatment with 20 ng of picrotoxin, 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. However, similar inhibition in the lateral septum attenuates active avoidance of anxiogenic stimuli (i.e., decreased burying behavior), but not passive avoidance 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.