Frequency-dependence of serotonin autoreceptor but not alpha 2-adrenoceptor inhibition of [3H]-serotonin release in rat hypothalamic slices

Naunyn Schmiedebergs Arch Pharmacol. Jan-Feb 1989;339(1-2):60-4. doi: 10.1007/BF00165127.


The overflow of tritium from stimulated rat hypothalamic slices preincubated with [3H]-serotonin (5-HT) was significantly enhanced by reducing the frequency of stimulation from 3 Hz to 1 Hz while keeping the number of impulses constant. The 5-HT receptor agonist 5-methoxytryptamine inhibited in a concentration-dependent manner the electrically-evoked release of [3H]-5-HT with IC50 values of 560 nmol/l and of 34 nmol/l when the stimulations were delivered at 3 Hz and 1 Hz, respectively. The terminal 5-HT autoreceptor antagonist methiothepin enhanced in a concentration-dependent manner the electrically-evoked release of [3H]-5-HT and this effect was greater at a frequency of stimulation of 3 Hz than at 1 Hz. In the same paradigm, the 5-HT reuptake inhibitors citalopram and paroxetine did not alter the overflow of radioactivity elicited by stimulation at 3 Hz but significantly decreased it at 1 Hz. In the presence of 5-HT autoreceptor blockade achieved with methiothepin, citalopram increased the overflow of [3H]-5-HT to the same extent at 1 Hz and at 3 Hz. The IC50 values for inhibition of [3H]-5-HT release by the selective alpha 2-adrenoceptor agonist UK 14.304 were 35 nmol/l at 3 Hz and 30 nmol/l at 1 Hz. It is concluded that modulation of 5-HT release by 5-HT autoreceptors, but not by alpha 2-adrenoceptors is dependent on the synaptic concentration of 5-HT as a function of the frequency of depolarization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methoxytryptamine / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Antihypertensive Agents / pharmacology
  • Brimonidine Tartrate
  • Citalopram / pharmacology
  • Electric Stimulation
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism*
  • Hypothalamus / physiology
  • In Vitro Techniques
  • Male
  • Paroxetine
  • Piperidines / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism*
  • Serotonin / metabolism*


  • Adrenergic alpha-Antagonists
  • Antihypertensive Agents
  • Piperidines
  • Quinoxalines
  • Receptors, Serotonin
  • Citalopram
  • Serotonin
  • 5-Methoxytryptamine
  • Paroxetine
  • Brimonidine Tartrate