Effects of 5-HT receptor agonists on depolarization-induced [3H]-noradrenaline release in rabbit hippocampus and human neocortex

Br J Pharmacol. 1995 Sep;116(2):1769-74. doi: 10.1111/j.1476-5381.1995.tb16661.x.


1. The present study attempted to determine whether noradrenaline (NA) release in rabbit hippocampus and human neocortex is modulated by presynaptic 5-hydroxytryptamine (5-HT) receptors. 2. Slices of rabbit hippocampus and human neocortex, loaded with [3H]-noradrenaline ([3H]-NA) were superfused and the effects of 5-hydroxytryptamine (5-HT) receptor ligands on electrically evoked [3H]-NA release were investigated. 3. In rabbit hippocampus, 5-HT, 5-carboxamidotryptamine (5-CT; 32 microM) and 2-CH3-5-HT (32 microM) increased [3H]-NA release elicited with 360 pulses/3 Hz. Facilitation of transmitter release was not influenced by the 5-HT3 receptor antagonist, tropisetron but was prevented by the alpha 2-adrenoceptor antagonist, rauwolscine. When autoinhibition was avoided by stimulating the tissue with 4 pulses/100 Hz (pseudo-one pulse-(POP) stimulation), 2-CH3-5-HT decreased evoked transmitter release, whereas 5-HT and 5-CT had no effect. Inhibition caused by 2-CH3-5-HT was not affected by tropisetron but counteracted by the alpha 2-adrenoceptor ligands, clonidine and rauwolscine. Inhibition caused by clonidine was diminished in the presence of 5-CT or 2-CH3-5-HT. 4. In human neocortex, [3H]-NA release elicited with 360 pulses/3 Hz was increased by 10 microM 5-HT and 32 microM 5-CT, whereas 2-CH3-5-HT was ineffective. [3H]-NA release evoked with a modified POP stimulation (2 bursts of 4 pulses/100 Hz, 3.5 min apart) was not affected by 2-CH3-5-HT or 5-CT. 5. The present results indicate that 5-HT, 2-CH3-5-HT and 5-CT can act on presynaptic alpha 2-autoreceptors as partial agonists (2-CH3-5-HT; in rabbit hippocampal tissue) or antagonists (5-HT and 5-CT; in tissue of rabbit hippocampus and human neocortex). Furthermore the existence of autoinhibition dictates whether these drugs cause facilitation of release, inhibition or have no effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Distribution
  • Animals
  • Cerebral Cortex / drug effects*
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects*
  • Humans
  • Norepinephrine / metabolism*
  • Rabbits
  • Receptors, Serotonin / drug effects*
  • Serotonin / analogs & derivatives*
  • Serotonin / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*


  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Serotonin
  • 5-carboxamidotryptamine
  • Norepinephrine