The amygdala mediates the anxiolytic-like effect of the neurosteroid allopregnanolone in rat.
The neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) possesses clear anxiolytic-like effects. Other neurosteroids namely pregnenolone sulfate (PREG-S) and dehydroepiandrosterone sulfate (DHEA-S) influence anxiety-related behavior differently. In the present study, the implication of the amygdala, a key structure in mechanisms of fear and anxiety, was investigated as a potential neural substrate for the effects of neurosteroids on anxiety-like behavior in rat. Animals implanted with bilateral cannulae aimed at the central nucleus of the amygdala (CeA) and infused with neurosteroids, were tested in two animal models of anxiety. Allopregnanolone (8 microg/side) produced a significant increase in responding suppressed by punishment in the conflict test. In the elevated plus maze, allopregnanolone (8 microg/side) induced a significant increase in the time spent and the number of entries in open arms compared with the vehicle-infused controls. No significant changes in punished and unpunished responding of the conflict test were observed with PREG-S (0.001-8 microg/side) and DHEA-S (2-8 microg/side) administered into the CeA or into the lateral ventricle (1-20 microg). The results reveal the lack of activity of PREG-S and DHEA-S in the operant conflict test, but suggest that the central nucleus of the amygdala is a key region involved in the mechanisms underlying the anxiolytic-like action of allopregnanolone.
Akwa
Y
Y
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. yakwa@kb.inserm.fr
Purdy
R H
RH
Koob
G F
GF
Britton
K T
KT
D000679:Amygdala / Q000033:anatomy & histology / Q000502:physiology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003220:Conflict, Psychological; D019314:Dehydroepiandrosterone Sulfate / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007267:Injections; D007276:Injections, Intraventricular; D010052:Ovariectomy; D011280:Pregnanolone / Q000008:administration & dosage / Q000494:pharmacology*; D011284:Pregnenolone / Q000008:administration & dosage / Q000494:pharmacology; D011678:Punishment; D051381:Rats; D017208:Rats, Wistar
D014151:Anti-Anxiety Agents; D019314:Dehydroepiandrosterone Sulfate; D011284:Pregnenolone; D011280:Pregnanolone