The sites of origin brain stem neurotensin and serotonin projections to the rodent nucleus raphe magnus

Abstract

The combined horseradish peroxidase retrograde transport-peroxidase-antiperoxidase immunohistochemical procedure was utilized in the present study to ascertain the sites of origin of serotonin and neurotensin projections to the rodent nucleus raphe magnus. The major serotonin inputs to the raphe magnus arise from the B-8 and B-9 groups of Dahlstrom and Fuxe (Dahlstrom, A., and K. Fuxe (1964) Acta Physiol. Stand. Suppl. 232 62: l-55), the nucleus reticularis paragigantocellularis, and the nucleus reticularis gigantocellularis pars (Y. Neurotensinergic projections to the raphe magnus originate predominantly from the periaqueductal gray, the nucleus solitarius, the dorsal and ventral parabrachial nuclei, and the nucleus cuneiformis. The periaqueductal gray and the nucleus paragigantocellularis were found to provide both a neurotensin and a serotonin projection to this raphe nucleus. The present results indicate that several brain stem nuclei, which have been implicated previously in endogenous analgesia mechanisms, provide serotonergic and neurotensinergic input to the nucleus raphe magnus. Reynolds (1969) and Mayer and Liebeskind (1974) were among the first investigators to demonstrate that potent analgesia could be produced by electrical brain stimulation in freely moving animals. Most of the early studies of centrally induced analgesia focused on the midbrain periaqueductal gray (PAG) from which stimulation-produced analgesia was best elicited. Subsequent studies have demonstrated that stimulation of the medullary nucleus raphe magnus (NRM), a source of serotonin neurons, also produces potent analgesia (Fields and Basbaum, 1978; Oliveras et al., 1979). Moreover, it has been shown that stimulation of the PAG alters the activity of cells in the NRM (Pomeroy and Behbehani, 1979) and that lesions of the NRM produce a pronounced decrease in nociceptive threshold (Proudfit, 1981). Both the analgesic action of opiates and electrical stimulation of the PAG are blocked by lesion of the dorsolateral part of the spinal cord (Basbaum et al., 1977). Since (I) the PAG sends very few direct projections to the spinal cord and (2) a PAG-NRM projection was demonstrated (Ruda,

Genetically expressed transneuronal tracer reveals direct and indirect serotonergic descending control circuits

“…Anti-5HT antibodies were raised in rats using serotonin conjugated to hemocyanin as immunogen. The patterns of 5HT and TH-immunoreactivity that we observed with these antisera are very comparable to those reported in many other studies of the distribution of 5HT and TH in the mouse and rat brain (Dahlström and Fuxe, 1964;Beitz, 1982;Vander-Horst and Ulfhake, 2006). Anti-β-gal antibodies were produced by hyperimmunizing rabbits with the enzyme β-gal from Escherichia coli.…”

“…Author Manuscript mouse and rat brain (Dahlström and Fuxe, 1964;Beitz, 1982; Vander-Horst and Ulfhake, 2006). Anti-β-gal antibodies were produced by hyperimmunizing rabbits with the enzyme β-gal from Escherichia coli.…”

“…Given that we found that many of the non-5HT spinally projecting neurons of the medulla lie downstream of 5HT neurons, we next addressed the source of this 5HT input. Although it has been established that there is a limited dorsal raphe 5HT projection to the medulla (Beitz, 1982), here we could also address the possibility that these 5HT neurons indirectly regulate medullary neurons through their connections within the PAG.…”

Zentrale Schmerzverarbeitung bei chronischem Rückenschmerz

“…Das System funktioniert durch die schnelle, automatische Gegenregulation zur Kontrolle nozizeptiver afferenter Information via absteigender inhibitorischer Bahnen. Das PAG erhält u. a. Signale vom Frontalkortex [40], Hypothalamus [6], dem anterioren Insulakortex [21] und den Amygdalae [20], die alle auch mit der Schmerzverarbeitung assoziiert wurden. Das kaudale PAG leitet die Informationen weiter zur RVM, die diese ihrerseits zu den schmerzübertragenden Neuronen des Hinterhorns und der Trigeminusganglien weiterleitet.…”

Multitasking with neurotensin in the central nervous system

“…Labeled NT binding sites are also located principally in the superficial laminae of the dorsal horn and spinal trigeminal nucleus in the rat [201] and human [202]. Similarly, numerous NT-IR cell bodies and fibers have been described in the rat PAG, and the PAG sends a major NTergic projection to the RVM [203][204][205]. NTR-1 is expressed at weak to moderate levels in dendrites and cell bodies both dorsal and ventral to the cerebral aqueduct in the PAG, and on serotonin neurons in the nucleus raphe magnus and dorsalis [92,93,206].…”