Dorsal raphe nucleus

The dorsal raphe nucleus consists of rostral and caudal subdivisions. The rostral aspect of the dorsal raphe is further divided into interfascicular, ventral, ventrolateral and dorsal subnuclei. The projections of the dorsal raphe have been found to vary topographically, and thus the subnuclei differ in their projections. An increased number of cells in the lateral aspects of the dorsal raphe is characteristic of humans and other primates. The dorsal raphe is the largest serotonergic nucleus and provides a substantial proportion of the serotonin innervation to the forebrain. Serotonergic neurons are found throughout the dorsal raphe nucleus and tend to be larger than other cells. A substantial population of cells synthesising substance P are found in the rostral aspects, many of these co-express serotonin and substance P. There is also a population of catecholamine synthesising neurons in the rostral dorsal raphe, and these cells appear to be relatively large. The nucleus raphe dorsalis is rich in serotonin 5-HT1a autoreceptors and it is believed that it is the action of serotonin-specific reuptake inhibitors (SSRIs) in this region that is responsible for the latency of SSRI antidepressant effect.

Ten percent of the axons from the nucleus raphe dorsalis have been shown to project to the amygdala, while only medium cells seem to project to the caudate and putamen. The nucleus raphe dorsalis has also been implicated in naloxone-induced morphine withdrawal. It is known that endogenous opiate receptors exist on the nucleus raphe dorsalis, and that it is a focal point as an ascending and descending regulator. Pourshanazari et al showed in their 2000 paper that electrical stimulation of the nucleus raphe dorsalis can partially alleviate morphine withdrawal symptoms via electrical stimulation of the raphe nucleus in question (Pourshanazari, A.A. ; Alaei ; Rafati ; Effects of Electrical Stimulation of Nucleus Raphe Dorsalis on initiation of morphine self administration in rats. Medical Journal of Islamic Academy of Sciences 13:2, 63-67, 2000). These are fascinating results; however no control was provided for the spread of electrical charge to other parts of the brain stem. It is quite possible that the charge spread to the nucleus raphe magnus and induced analgesia upon the rats. Knowing that the spread of charge across such a short area is very plausible, as is an alternate connection to the raphe magnus, these results could be called into question. Wu M.F. et al. studied the raphe dorsalis as it pertained to narcolepsy, this is logical, as the raphe nuclei have been known to play a role in the sleep/wake cycle. Cataplexy is the symptom of narcolepsy when full awareness of the environment is maintained, but all muscle tone is lost. This has thought to be a dissociation of what normally happens during REM sleep, when all muscle tone is lost except for the eyes. The raphe dorsalis have been known to project to the lateral hypothalamus, along with the locus coeruleus and the tuberomammillary nucleus. The neurotransmitters of these three aforementioned nuclei, which project to the lateral hypothalamus, are serotonin, Norepinephrine and histamine respectively. These neurotransmitters are fully active during waking hours, partially active during non-REM sleep, and have almost ceased during REM sleep. In cats with pontine lesions, their normal atonia is not present, the raphe dorsalis is fully active, as opposed to the cessation of action under normal conditions. A muscle relaxant, known as Mephenesin, reduces to activity of the dorsal nucleus, as well as microinjections of carbachol (which induces atonia while awake) (Wu et al. Activity of Dorsal raphe cells across the sleep-waking cycle during cataplexy in narcoleptic dogs. Journal of Physiology. 2004 Jan 1;554 (Pt 1):202-15).