Compartmentation of alpha 1 and alpha 2 GABA(A) receptor subunits within rat extended amygdala: implications for benzodiazepine action.
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.
Kaufmann
Walter A
WA
Centre for Molecular Biology and Neuroscience, Department of Anatomy, University of Oslo, N-0317 Oslo, Norway.
Humpel
Christian
C
Alheid
George F
GF
Marksteiner
Josef
J
D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001569:Benzodiazepines / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D021122:Protein Subunits / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D053381:Secretogranin II; D012686:Septal Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013377:Substantia Innominata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D009479:Neuropeptides; D021122:Protein Subunits; D011963:Receptors, GABA-A; D053381:Secretogranin II; D001569:Benzodiazepines; C081159:secretoneurin