The GABA&#946; receptor as a target for antidepressant drug action.
Preclinical and clinical data suggest that a modification in GABA(B) receptor expression and function may contribute to the symptoms of major depression and the response to antidepressants. This includes laboratory animal experiments demonstrating that antidepressants modify brain GABA(B) receptor expression and function and that GABA(B) receptor antagonists display antidepressant potential in animal models of this condition. Clinical and post-mortem studies reveal changes in GABAergic transmission associated with depression as well as depression-related changes in GABA(B) subunit expression that are localized to the cortical depression network. Detailed in this review are the preclinical and clinical data implicating a role for the GABA(B) receptor system in mediating symptoms of this disorder and its possible involvement in the response to antidepressants. Particular emphasis is placed on clinical and post-mortem studies, including previously unpublished work demonstrating regionally-selective modifications in GABA(B) receptor subunit expression in brain samples obtained from depressed subjects. Together with the earlier preclinical studies, these new data point to a role for the GABA(B) system in major depression and support the antidepressant potential of GABA(B) receptor antagonists.
Ghose
Subroto
S
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Winter
Michelle K
MK
McCarson
Kenneth E
KE
Tamminga
Carol A
CA
Enna
Salvatore J
SJ
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D018080:Receptors, GABA-B / Q000187:drug effects*
D000928:Antidepressive Agents; D018756:GABA Antagonists; D018080:Receptors, GABA-B