GABA and circadian timekeeping: implications for manic-depression and sleep disorders

Med Hypotheses. 1986 Feb;19(2):185-98. doi: 10.1016/0306-9877(86)90059-9.

Abstract

Circadian rhythms, evident in a wide variety of physiological and behavioural parameters, are under the control of central neural pacemakers, the best characterized of which is the suprachiasmatic nucleus of the hypothalamus. The neurophysiological mechanisms involved in central pacemaker function are unknown. Recent biochemical, pharmacological and behavioural evidence suggests that the inhibitory transmitter gamma-aminobutyric acid (GABA), present in the small interneurones of the suprachiasmatic nucleus, plays an important role in circadian timekeeping. This has enabled the formulation of strategies for treatment of patients with manic depressive illness and certain sleep disorders in which disorders of circadian timekeeping may be fundamental.

MeSH terms

  • 4-Aminobutyrate Transaminase / antagonists & inhibitors
  • Acetylcholine / physiology
  • Aldehyde Oxidoreductases / antagonists & inhibitors
  • Animals
  • Benzodiazepines / pharmacology
  • Benzodiazepines / therapeutic use
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / physiopathology*
  • Carbamazepine / pharmacology
  • Carbamazepine / therapeutic use
  • Circadian Rhythm* / drug effects
  • Enzyme Induction / drug effects
  • Glutamate Dehydrogenase / biosynthesis
  • Humans
  • Hypothalamus, Middle / physiopathology
  • Lithium / pharmacology
  • Lithium / therapeutic use
  • Models, Biological*
  • Receptors, GABA-A / physiology
  • Sleep Wake Disorders / drug therapy
  • Sleep Wake Disorders / physiopathology*
  • Succinate-Semialdehyde Dehydrogenase
  • Suprachiasmatic Nucleus / physiopathology
  • Valproic Acid / pharmacology
  • Valproic Acid / therapeutic use
  • gamma-Aminobutyric Acid / physiology*

Substances

  • Receptors, GABA-A
  • Benzodiazepines
  • Carbamazepine
  • gamma-Aminobutyric Acid
  • Valproic Acid
  • Lithium
  • Aldehyde Oxidoreductases
  • ALDH5A1 protein, human
  • Succinate-Semialdehyde Dehydrogenase
  • Glutamate Dehydrogenase
  • 4-Aminobutyrate Transaminase
  • Acetylcholine