GABA receptors inhibited by benzodiazepines mediate fast inhibitory transmission in the central amygdala.
The amygdala is intimately involved in emotional behavior, and its role in the generation of anxiety and conditioned fear is well known. Benzodiazepines, which are commonly used for the relief of anxiety, are thought to act by enhancing the action of the inhibitory transmitter GABA. We have examined the properties of GABA-mediated inhibition in the amygdala. Whole-cell recordings were made from neurons in the lateral division of the central amygdala. Application of GABA evoked a current that reversed at the chloride equilibrium potential. Application of the GABA antagonists bicuculline or SR95531 inhibited the GABA-evoked current in a manner consistent with two binding sites. Stimulation of afferents to neurons in the central amygdala evoked an IPSC that was mediated by the release of GABA. The GABA(A) receptor antagonists bicuculline and picrotoxin failed to completely block the IPSC. The bicuculline-resistant IPSC was chloride-selective and was unaffected by GABA(B)-receptor antagonists. Furthermore, this current was insensitive to modulation by general anesthetics or barbiturates. In contrast to their actions at GABA(A) receptors, diazepam and flurazepam inhibited the bicuculline-resistant IPSC in a concentration-dependent manner. These effects were fully antagonized by the benzodiazepine site antagonist Ro15-1788. We conclude that a new type of ionotropic GABA receptor mediates fast inhibitory transmission in the central amygdala. This receptor may be a potential target for the development of new therapeutic strategies for anxiety disorders.
Delaney
A J
AJ
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia.
Sah
P
P
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005479:Flurazepam / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D005998:Glycine / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009557:Nipecotic Acids / Q000494:pharmacology; D009567:Nitrazepam / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D013331:Strychnine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D009557:Nipecotic Acids; D010091:Oximes; D011724:Pyridazines; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C078793:NNC 711; D005680:gamma-Aminobutyric Acid; C049853:gabazine; D009567:Nitrazepam; D013331:Strychnine; D005479:Flurazepam; D005998:Glycine; D001640:Bicuculline