Neurosteroid modulation of GABAergic neurotransmission in the central amygdala: a role for NMDA receptors.
The neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone or ALLO) positively modulates GABA(A) receptors, an action that may contribute to the anxiolytic effects of ALLO. Recent evidence suggests that ALLO's anxiolytic effects appear to be mediated by the amygdala, a key neural structure for emotional and cognitive behaviors. However, little is known regarding ALLO effects on amygdala physiology. We therefore explored ALLO effects on GABA neurotransmission in the central nucleus (Ce) of the amygdala, a major output nucleus involved in fear and anxiety. We recorded evoked GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) in Ce neurons using whole-cell patch clamp techniques. We observed that ALLO significantly reduced the amplitude of evoked GABA(A) receptor-mediated IPSCs. However, the effect of ALLO was occluded by the NMDA receptor antagonist D-APV. D-APV alone also reduced evoked IPSCs in Ce neurons. These results suggest that ALLO-induced reduction of GABAergic transmission in Ce appears to depend on neural network activity, possibly involving an NMDA receptor-mediated mechanism. These ALLO effects on GABAergic transmission in the central amygdala may play a role in mediating its anxiolytic actions.
Wang
Chunsheng
C
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, NC 27705, USA.
Marx
Christine E
CE
Morrow
A Leslie
AL
Wilson
Wilkie A
WA
Moore
Scott D
SD
D000679:Amygdala / Q000166:cytology / Q000502:physiology*; D000704:Analysis of Variance; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000528:radiation effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000777:Anesthetics; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010852:Picrotoxin; D011280:Pregnanolone; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid