Selective increase of alpha2A-adrenoceptor agonist binding sites in brains of depressed suicide victims

J Neurochem. 1998 Mar;70(3):1114-23. doi: 10.1046/j.1471-4159.1998.70031114.x.

Abstract

The alpha2A- and alpha2C-adrenoceptor subtypes were evaluated in postmortem brains from suicides with depression (n = 22), suicides with other diagnoses (n = 12), and controls (n = 26). Membrane assays with the antagonist [3H]RX821002 (2-[3H]methoxyidazoxan) suggested the presence of alpha2A-adrenoceptors in the frontal cortex and both alpha2C-adrenoceptors and alpha2A-adrenoceptors in the caudate. The proportions in caudate were similar in controls (alpha2A, 86%; alpha2C, 14%), depressed suicides (alpha2A, 91%; alpha2C, 9%), and suicides with other diagnoses (alpha2A, 88%; alpha2C, 12%). Autoradiography of [3H]RX821002 binding under alpha(2B/C)-adrenoceptor-masking conditions confirmed the similar densities of alpha2A-adrenoceptors in the cortex, hippocampus, and striatum from controls and suicides. In the frontal cortex of depressed suicides, competition of [3H]RX821002 binding by (-)-adrenaline revealed a greater proportion (61 +/- 9%) of alpha2A-adrenoceptors in the high-affinity conformation for agonists than in controls (39 +/- 5%). Simultaneous analysis with the agonists [3H]clonidine and [3H]UK14304 and the antagonist [3H]RX821002 in the same depressed suicides confirmed the enhanced alpha2A-adrenoceptor density when evaluated by agonist, but not by antagonist, radioligands. The results indicate that depression is associated with a selective increase in the high-affinity conformation of the brain alpha2A-adrenoceptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Adult
  • Autoradiography
  • Binding, Competitive
  • Brain Chemistry / physiology*
  • Brimonidine Tartrate
  • Cell Membrane / chemistry
  • Clonidine / pharmacology
  • Depression / metabolism*
  • Female
  • Frontal Lobe / chemistry
  • Frontal Lobe / metabolism
  • Humans
  • Idazoxan / analogs & derivatives
  • Idazoxan / pharmacology
  • Male
  • Middle Aged
  • Quinoxalines / pharmacology
  • Receptors, Adrenergic, alpha-2 / metabolism*
  • Suicide*
  • Tritium

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Quinoxalines
  • Receptors, Adrenergic, alpha-2
  • Tritium
  • Brimonidine Tartrate
  • 2-methoxyidazoxan
  • Clonidine
  • Idazoxan