The amygdala mediates the anxiolytic-like effect of the neurosteroid allopregnanolone in rat

The neurosteroid allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one) possesses clear anxiolytic-like effects. Other neurosteroids namely pregnen olone sulfate (PREG-S) and dehydroepiandrosterone sulfate (DH EA-S) influen ce anxiety-related behavior differently. In the present study, the implicat ion of the amygdala, a key structure in mechanisms of fear and anxiety, was investigated as a potential neural substrate for the effects of neurostero ids on anxiety-like behavior in rat. Animals implanted with bilateral cannu lae aimed at the central nucleus of the amygdala (CeA) and infused with neu rosteroids, were tested in two animal models of anxiety. Allopregnanolone ( 8 mu g/side) produced a significant increase in responding suppressed by pu nishment in the conflict test. In the elevated plus maze, allopregnanolone (8 mu g/side) induced a significant increase in the time spent and the numb er of entries in open arms compared with the vehicle-infused controls. No s ignificant changes in punished and unpunished responding of the conflict te st were observed with PREG-S (0.001-8 mu g/side) and DHEA-S (2-8 mu g/side) administered into the CeA or into the lateral ventricle (1-20 mu g). The r esults reveal the lack of activity of PREG-S and DHEA-S in the operant conf lict rest, but suggest that the central nucleus of the amygdala is a key re gion involved in the mechanisms underlying the anxiolytic-like action of al lopregnanolone. (C) 1999 Elsevier Science B.V. All rights reserved.