Histamine H1 receptors in rat dorsal raphe nucleus: pharmacological characterisation and linking to increased neuronal activity

Brain Res. 2002 Nov 8;954(2):247-55. doi: 10.1016/s0006-8993(02)03352-8.


In this work we studied the presence of histamine H(1) receptors in the rat dorsal raphe nucleus (DRN) and the effect of their activation on the activity of presumed serotonergic DRN neurones. [(3)H]-Mepyramine bound to DRN membranes with best-fit values of 107+/-13 fmol/mg protein for maximum binding (B(max)) and 1.2+/-0.4 nM for the equilibrium dissociation constant (K(d)). In DRN slices labelled with [(3)H]-inositol and in the presence of 10 mM LiCl, histamine stimulated the accumulation of [(3)H]-inositol phosphates ([(3)H]-IPs) with maximum effect 172+/-6% of basal and EC(50) 3.2+/-1.3 microM. [(3)H]-IPs accumulation induced by 100 microM histamine (162+/-5% of basal) was markedly, but not fully blocked by the selective H(1) antagonist mepyramine (300 nM; 64+/-6% inhibition). The simultaneous addition of mepyramine and the selective H(2) antagonist ranitidine (10 microM) abolished histamine-induced [(3)H]-IPs accumulation. The presence of H(2) receptors was confirmed by [(3)H]-tiotidine binding and by the determination of histamine-induced [(3)H]-cyclic AMP formation. Extracellular single-unit recording in brain stem slices showed that the exposure to histamine resulted in a marked increase in the firing rate of DRN presumed serotonergic neurones (471+/-10% of basal), that was dependent on the concentration of the agonist (EC(50) 4.5+/-0.3 microM). The action of histamine was not affected by the H(2) antagonist tiotidine (2 microM) but was fully prevented by 1 microM mepyramine. Taken together, our results indicate that histamine modulates the firing of DRN presumed serotonergic neurones through the activation of H(1) receptors coupled to phosphonositide hydrolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Brain Stem / metabolism
  • Cimetidine / analogs & derivatives*
  • Cimetidine / pharmacology
  • Histamine / pharmacology
  • Histamine H1 Antagonists / pharmacology
  • Histamine H2 Antagonists / pharmacology
  • Inositol Phosphates / metabolism
  • Male
  • Neurons / drug effects
  • Neurons / metabolism*
  • Pyrilamine / pharmacology
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Histamine H1 / drug effects
  • Receptors, Histamine H1 / metabolism*
  • Serotonin / metabolism


  • Histamine H1 Antagonists
  • Histamine H2 Antagonists
  • Inositol Phosphates
  • Receptors, Histamine H1
  • Serotonin
  • Cimetidine
  • Histamine
  • tiotidine
  • Pyrilamine