GABAergic hypotheses of anxiety and depression: focus on GABA-B receptors.
Depression and anxiety are psychiatric disorders with high morbidity and comorbidity. Because of multiple adverse effects of existing drugs and a low efficacy, therapy for a substantial number of patients is unsatisfactory. It is widely accepted that gamma-aminobutyric acid (GABA) is the primary inhibitory transmitter substance in the mammalian central nervous system. Data are accumulating that the recently cloned GABAB receptors might become a target for the development of new antidepressant and/or anxiolytic drugs. The existing data support the hypothesis that agonists and particularly positive modulators of GABAB receptors (but not GABAB receptor antagonists) may be anxiolytic drugs in the future. The experiments demonstrate that the most consistent finding following chronic administration of antidepressants is an increase in GABAB receptor function, with or without a change in receptor binding or subunit expression. Data are accumulating in preclinical studies that show that antagonists (but not agonists) of GABAB receptors may have antidepressant effects.
Pilc
Andrzej
A
Institute of Public Health, Collegium Medicum, Jagiellonian University, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Nowak
Gabriel
G
D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology; D001921:Brain / Q000187:drug effects; D002986:Clinical Trials as Topic; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D006801:Humans; D008958:Models, Molecular; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid