5-HT1D Receptors Regulate 5-HT Release in the Rat Raphe Nuclei

Abstract

The aim of the present study was to characterize the pharmacological profile of 5-hydroxytryptamine (5-HT) receptors modulating 5-HT release in the mesencephalic raphe region. In a first series of experiments, differential normal pulse voltammetry and nafion-coated electrodes were used to measure extracellular 5-HT in the dorsal 5-carboxy-amiditryptamine (5-CT) and the 5-HTrnno agonist sumatriptan (1-1,000 nM) induced a concentration-dependent inhibition of the electrically evoked release of [3H}5-HT from preloaded raphe slices. 8-OH-DPAT (100 nM) produced an inhibitory effect similar to that of sumatriptan (100 nM

Evidence that 5‐hydroxytryptamine release in rat dorsal raphé nucleus is controlled by 5‐HT1A, 5‐HT1B and 5‐HT1D autoreceptors

“…The rat is not generally held to have functional 5-HTlD receptors, although mRNA for the rat homologue of the 5-HTID, receptor is found in the DRN (Hamblin et al, 1992) and it has been tentatively suggested that there may be functional 5-HTlD receptors in the rat DRN (Pineyro et al, 1994). However these conclusions were largely based on the use of mianserin as a 5-HTID antagonist, a drug with only modest selectivity over 5-HTlB receptors (Hoyer et al, 1994).…”

Inverse Agonists and Serotonergic Transmission From Recombinant, Human Serotonin (5-HT)1B Receptors to G-Protein Coupling and Function in Corticolimbic Structures in vivo

“…Seventh, for inverse agonist actions to be detected, the receptor must be present in a constitutively active state and, ideally; endogenous agonist(s) should not be present. However, in vivo, 5-HT is spontaneously released both at the dendritic and terminal level (Piñeyro et al 1995). Indeed, basal dialysate levels of 5-HT are reliably measurable, suggesting that 5-HT is available to pre-and postsynaptic receptors ).…”

“…The 5-HT 1A , 5-HT 1B , and 5-HT 1D receptors are of particular interest inasmuch as they are localized both postsynaptically to serotonergic neurones as well as presynaptically, as inhibitory autoreceptors on their dendrites (5-HT 1A and a minor population of 5-HT 1B/1D sites) and terminals (5-HT 1B sites) (Piñeyro et al 1995;Starkey and Skingle 1994). It might, thus, be hypothesized that inverse agonist actions at 5-HT 1A , 5-HT 1B , and/or 5-HT 1D autoreceptors may facilitate serotonergic transmission (Gaster et al 1998;Moret and Briley 1993;Roberts et al 1997).…”

The Potential Role of 5-HT1D Receptors in the Pathophysiology and Treatment of Obsessive-Compulsive Disorder

“…24 " 26 Indeed, in vitro administration of sumatriptan, a 5-HT 1D agonist, induced inhibition of electrically evoked release of 5-HT from rat brain raphe slices. 25 Consequently, it could be assumed that chronic administration is associated with rapid decrease in 5-HT tone and thus an improvement in obsessive-compulsive symptoms. 2 7 Sumatriptan is an antimigraine agent whose pharmacological effect appears to be related to the 5-HT 1D receptors and is approximately 5 times less potent at 5-HT 1B receptors and 20 times less potent at 5-HT 1A receptors, having only a minor affinity at 5-HT 1E receptors.…”