Neurosteroid modulation of GABAergic neurotransmission in the central amygdala: A role for NMDA receptors

• Published in: Neuroscience letters Vol. 415; no. 2; pp. 118 - 123
• Main Authors: Wang, Chunsheng, Marx, Christine E., Morrow, A. Leslie, Wilson, Wilkie A., Moore, Scott D.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 26.03.2007; Elsevier
• Subjects: Allopregnanolone; Amygdala; Amygdala - cytology; Amygdala - physiology; Analysis of Variance; Anesthetics - pharmacology; Animals; Animals, Newborn; Biological and medical sciences; Dose-Response Relationship, Drug; Drug Interactions; Electric Stimulation; Excitatory Amino Acid Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; GABA A; GABA Antagonists - pharmacology; gamma-Aminobutyric Acid - metabolism; In Vitro Techniques; Inhibitory Postsynaptic Potentials - drug effects; Inhibitory Postsynaptic Potentials - physiology; Male; Membrane Potentials - drug effects; Membrane Potentials - radiation effects; Neurons - drug effects; Neurons - physiology; Neurosteroid; NMDA; Patch clamp; Patch-Clamp Techniques; Picrotoxin - pharmacology; Pregnanolone - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - physiology; Synaptic Transmission - drug effects; Synaptic Transmission - radiation effects; Vertebrates: nervous system and sense organs; NMDA; Patch clamp; GABA A; Neurosteroid; Amygdala; Allopregnanolone; Metabolite; Central nervous system; Electrophysiology; Patch clamp method; Basal ganglion; Glutamate receptor; Ovarian hormone; Encephalon; GABAA; Progesterone; Sex steroid hormone; NMDA receptor; Neurotransmission
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2007.01.004

The neurosteroid 3α-hydroxy-5α-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.