Subtype-specificity of the presynaptic alpha 2-adrenoceptors modulating hippocampal norepinephrine release in rat

Brain Res. 1995 Mar 20;674(2):238-44. doi: 10.1016/0006-8993(94)01447-p.


In vivo brain microdialysis and high-performance liquid chromatography with electrochemical detection were used to study the effect of different selective alpha 2-antagonists on hippocampal norepinephrine (NE) release in freely moving awake rat. Systemic administration (0.5 mg/kg i.p.) of either the alpha 2AD-antagonist BRL 44408 or the alpha 2BC-antagonist ARC 239 did not significantly change the basal release of NE. At a higher dose (5 mg/kg i.p.) ARC 239 was still ineffective, whereas BRL 4408 caused a significant increase of the extracellular level of NF. Similar results were obtained from in vitro perfusion experiments. Rat hippocampal slices were loaded with [3H]NE and the electrical stimulation-evoked release of [3H]NE was determined. The alpha 2-antagonists were applied in a concentration range of 10(-8) to 10(-6) M, ARC 239 was ineffective, whereas BRL 44408 significantly increased the electrically induced release of [3H]NE. In agreement with the data of microdialysis and perfusion experiments, BRL 44408 displaced [3H]yohimbine from hippocampal and cortical membranes of rat brain with high affinity whereas ARC 239 was less effective. The pKi values of eight different alpha 2-adrenergic compounds showed a very good correlation (r = 0.98, slope = 1.11 P < 0.0001) in hippocampus and frontal cortex have the alpha 2-adrenoceptors have been characterized as alpha 2d-subtype. Our data indicate that hippocampal NE release in rat is regulated by alpha 2D-adrenoceptors, a species variation of the human alpha 2A-subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Chromatography, High Pressure Liquid
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • Male
  • Membranes / metabolism
  • Microdialysis
  • Norepinephrine / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-2 / metabolism*
  • Receptors, Presynaptic / metabolism*
  • Yohimbine / metabolism


  • Receptors, Adrenergic, alpha-2
  • Receptors, Presynaptic
  • Yohimbine
  • Norepinephrine