Compartmentation of alpha 1 and alpha 2 GABA(A) receptor subunits within rat extended amygdala: implications for benzodiazepine action

Brain Res. 2003 Feb 21;964(1):91-9. doi: 10.1016/s0006-8993(02)04082-9.

Abstract

The extended amygdala, a morphological and functional entity within the basal forebrain, is a neuronal substrate for emotional states like fear and anxiety. Anxiety disorders are commonly treated by benzodiazepines that mediate their action via GABA(A) receptors. The binding properties and action of benzodiazepines depend on the alpha-subunit profile of the hetero-pentameric receptors: whereas the alpha1 subunit is associated with benzodiazepine type I pharmacology and reportedly mediates sedative as well as amnesic actions of benzodiazepines, the alpha2 subunit confers benzodiazepine type II pharmacology and mediates the anxiolytic actions of benzodiazepines. We determined the localization of alpha1 and alpha2 subunits within the extended amygdala, identified by secretoneurin immunostaining, to define the morphological substrates for the diverse benzodiazepine actions. A moderate expression of the alpha1 subunit could be detected in compartments of the medial subdivision and a strong expression of the alpha2 subunit throughout the central subdivision. It is concluded that the alpha1 and alpha2 subunits are differentially expressed within the extended amygdala, indicating that this structure is compartmentalized with respect to function and benzodiazepine action.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amygdala / cytology
  • Amygdala / drug effects
  • Amygdala / metabolism*
  • Animals
  • Anxiety Disorders / drug therapy
  • Anxiety Disorders / metabolism
  • Anxiety Disorders / physiopathology
  • Benzodiazepines / pharmacology*
  • Fear / drug effects
  • Fear / physiology
  • Immunohistochemistry
  • Male
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuropeptides / metabolism
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Protein Subunits / drug effects
  • Protein Subunits / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism*
  • Secretogranin II
  • Septal Nuclei / cytology
  • Septal Nuclei / drug effects
  • Septal Nuclei / metabolism*
  • Substantia Innominata / cytology
  • Substantia Innominata / drug effects
  • Substantia Innominata / metabolism
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology

Substances

  • Neuropeptides
  • Protein Subunits
  • Receptors, GABA-A
  • Secretogranin II
  • Benzodiazepines
  • secretoneurin