Organization of serotonin 1A and 1B receptors in the nucleus of the solitary tract

Abstract

We utilized 3H-8-hydroxy-N,N-dipropyl-2-aminotetralin (3H-DPAT) and 125I-iodocyanopindolol (125I-CYP) to label serotonin (5HT) 1A and 5HT1B receptors, respectively, in sections of the rat brain after characterizing the pharmacologic specificity of these agents. We then used quantitative autoradiography to measure the concentrations of 5HT1A and 5HT1B receptors in individual subnuclei of the nucleus of the solitary tract (NTS) and adjacent structures of the dorsal vagal complex. The highest 5HT1A receptor concentrations were observed within the central and intermediate subnuclei of the NTS, with low quantities of 3H-DPAT binding sites observed in the hypoglossal nucleus and dorsal motor nucleus of the vagus. In contrast, the density of 5HT1B receptors was relatively homogeneous through all NTS subnuclei, with the highest concentrations localized within the ventrolateral subnucleus. The hypoglossal and dorsal motor nuclei had slightly higher 5HT1B receptor densities than the NTS subnuclei, whereas the area postrema had a very low density. These data suggest that 5HT1A receptors are organized in a manner consistent with the cytoarchitectural and hodological parcellation of the NTS into individual subnuclei. The high concentrations of 5HT1A receptors in the central and intermediate subnuclei suggest a role for these receptors in medullary reflex pathways subserving deglutition. The relatively high density of 5HT1B receptors in the ventrolateral subnucleus suggests that these receptors modulate respiratory neurons, whereas the diffuse organization of 5HT1B receptors in the remaining subnuclei suggests that they are associated with central 5HT afferent pathways to the NTS. Further studies will be required to understand the physiologic role of 5HT1 receptors within the NTS.

Postnatal Development of Serotonergic Innervation, 5-HT1AReceptor Expression, and 5-HT Responses in Rat Motoneurons

“…There have been no previous studies of 5-HT 1A receptor expression in the caudal brainstem of neonatal rats. However, consistent with our results, only low levels of 5-HT 1A receptor expression have been reported in the hypoglossal nucleus of adult rats by using a variety of techniques, including in situ hybridization, receptor binding, and immunohistochemistry (Manaker and Verderame, 1990;Chalmers and Watson, 1991;Pompeiano et al, 1992;Wright et al, 1995;Kia et al, 1996b). We showed that the 5-HT 1A receptor mRNA accumulation and 8-OH-DPAT binding paralleled each other, peaking at P7 from initially elevated levels at P0 before decreasing to low levels by P28; the decrease in receptor binding lagged somewhat the decrease in receptor mRNA levels.…”

“…Coronal sections (25 m) were cut in a cryostat, thaw-mounted onto twice gelatin-coated slides, and stored at Ϫ80°C. Sections were processed by following published protocols (Manaker and Verderame, 1990). They were warmed to room temperature, allowed to dry for 1 hr, and equilibrated in 0.17 M Tris-HCl, 4 mM CaCl 2 , and 0.1% ascorbate, pH 7.6, at room temperature for 30 min.…”

Inhibition of N‐ and P‐type calcium currents and the after‐hyperpolarization in rat motoneurones by serotonin.

“…In spinal neurones, 5-HT inhibited calcium current in a similar proportion of cells to that reported here for neonatal HMs, but the degree of inhibition by 5-HT in the responsive cells was greater (36% inhibition; Sah, 1990). In dorsal raphe neurones the effects of 5-HT on calcium current have been studied extensively (Penington et al 1991(Penington et al , 1992 (Manaker & Verderame, 1990). We have shown for the first time that both N-and P-type components of calcium current are modulated by 5-HT.…”

Mediation by 5‐HT3 receptors of an excitatory effect of 5‐HT on dorsal vagal preganglionic neurones in anaesthetized rats: an ionophoretic study

“…This suggests that although 5-HT3 receptors certainly can play a major role in mediating the excitatory action of 5-HT, the effects of 5-HT on DVN neurones may not be explained exclusively by an action on 5-HT3 receptors. Indeed, it has been previously demonstrated that 5-HTIA (Wang et al, 1995b) I 5-HT2 receptor antagonists (Wang et al, 1995a) can also attenuate the excitatory action of 5-HT on DVN neurones, and autoradiographic studies have demonstrated 5-HTIA, and 5-HT3 binding sites in the dorsal vagal nucleus (Dashwood et al, 1988;Manaker & Verderame, 1990;Pratt, et al, 1990;Thor et al, 1992;Steward et al, 1993;Leslie et al, 1994).…”