Locus coeruleus noradrenaline

Locus coeruleus (noradrenaline) highest lower lowest increased during W... 

Bouret, S. Sara, S. J. (2005). Network reset A simplified overarching theory of locus coeruleus noradrenaline function. Trends Neurosci., 28, 574-582. 

Pali), P and Stamford, JA (1994) Real-time monitoring of endogenous noradrenaline release in rat brain slices using fast cyclic voltammetry. 3. Selective detection of noradrenaline efflux in the locus coeruleus. Brain Res. 634 275-282. 

The enzyme /i-phenylethanolamine-A-methyl transferase, which is required to convert noradrenaline (NA) to adrenaline (Ad), is present in the CNS and there is histofluoro-metric evidence (positive staining with antibodies to that enzyme and to tyrosine hydroxylase and dopamine /i-hydroxylase as well) for adrenergic cell bodies in two groups (nuclei) alongside NA neurons of the locus coeruleus (EC) but ventral and lateral (Ci) and dorsal and medial (C2) to it. Projections go to the hypothalamus and in... 

Noradrenaline (norepinephrine) brainstem locus coeruleus neurons... 

Figure 2.4 Flip-flop switch model of wake and slow wave sleep active systems. Mutually inhibitory connections exist between GABAergic/Galaninergic slow wave sleep active neurons in the ventrolateral preoptic area (VLPO) of the anterior hypothalamus and aminergic neurons in the hypothalamus (histamine (HA) neurons in the tuberomammillary nucleus (TMN)) and brainstem (serotonin (5-HT) neurons in the dorsal raphe (DR) and noradrenaline (NA) neurons in the locus coeruleus (LC)). Orexinergic neurons in the perifornical hypothalamus (PFH) stabilize the waking state via excitation of the waking side of the flip-flop switch (aminergic neurons).

Figure 4.2 Model of the network responsible for paradoxical sleep onset and maintenance Abbreviations DRN, dorsal raphe nucleus 5-HT, serotonin LC, locus coeruleus NA, noradrenaline LDT, laterodorsal tegmental nucleus Ach, acetylcholine Me, magnocellular reticular nucleus Gly glycine DPMe, deep mesencephalic reticular nucleus PAG, periaqueductal gray DPGi, dorsal paragigantocellular reticular nucleus PPT, pedunculopontine nucleus PRN, pontine reticular nucleus SLD, sublaterodorsal nucleus Glu, glutamate Pef/HLA perifornical/lateral hypothalamic area Hcrt, hypocretin (i.e. orexin).

Devoto P., Flore G., Saba P Fa M., Gessa G. (2005). Stimulation of the locus coeruleus elicits noradrenaline and dopamine release in the medial prefrontal and parietal cortex. J. Neurochem. 92, 368-74. 

The neural structures involved in the promotion of the waking (W) state are located in the (1) brainstem [dorsal raphe nucleus (DRN), median raphe nucleus (MRN), locus coeruleus (LC), laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT), and medial-pontine reticular formation (mPRF)] (2) hypothalamus [tuberomammillary nucleus (TMN) and lateral hypothalamus (LH)[ (3) basal forebrain (BFB) (medial septal area, nucleus basalis of Meynert) and (4) midbrain ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) (Pace-Schott Hobson, 2002 Jones, 2003). The following neurotransmitters function to promote W (1) acetylcholine (ACh LDT/PPT, BFB) (2) noradrenaline (NA LC) (3) serotonin (5-HT DRN, MRN) (4) histamine (HA TMN) (5) glutamate (GLU mPRF, BFB, thalamus) (6) orexin (OX LH) and (7) dopamine (DA VTA, SNc) (Zoltoski et al, 1999 Monti, 2004). 

Recent experiments carried out by BOLME and coworkers (39) now raise the question of whether the receptors involved in reducing blood pressure are epinephrine receptors or noradrenaline receptors. These workers found that in rats small doses of yohimbine and piper-oxan blocked the blood pressure lowering effect of clonidine, but did not influence the clonidine-induced increase in flexor reflex activity. This effect on the reflex mechanism is possibly mediated by noradrenaline receptors which can be blocked only by higher doses of a-adrenolytic agents. HtfKFELT et al. (40) consider that epinephrine terminals possibly innervate noradrenaline cell bodies at the locus coeruleus. 

Mateo Y, Pineda J, Meana JJ. 1998. Somatodendritic alpha2-adrenoceptors in the locus coeruleus are involved in the in vivo modulation of cortical noradrenaline release by the antidepressant desipramine. J Neurochem 71(2) 790-798. 

Neuroanatomically both the locus coeruleus and the raphe nuclei project to the spinal cord where they gate sensory pathways from the skeletomuscular areas. As there is evidence that both noradrenaline and 5-HT are dysfunctional in depression, it is perhaps not surprising to find that the pain threshold is often reduced in patients with depression. Conversely, different types of antidepressants have been shown to have an antinociceptive effect in both rodent models of neuropathic pain, and clinically in fibromyalgia, chronic fatigue syndrome, postherpetic neuralgia and diabetic neuropathy. In general, it would appear that the dual action antidepressants (such as the TCAs and SNRIs) are more effective than the SSRIs. 

In animal experiments, stimulation of the locus coeruleus, a collection of noradrenalin-producing neurons located bilaterally in the pons area with... 

Engberg, G., and Eriksson, E. (1991) Effects of a-2-adrenoceptor agonists on locus coeruleus firing rate and brain noradrenaline turnover in EEDQ-treated rats. Naunyn Schmiedebergs Arch Pharmacol 343 472-477. 

Noradrenergic neurons at the locus coeruleus and serotonergic neurons at the raphe dorsalis complex project to the brain cortex and may play a role in AD. Drugs that raise serotonin levels, such as imipramine or zimeldine or a noradrenaline such as clonidine or guanfacine, have been used in AD [Mohr et al. 1989). Again, another chapter of this book deals with this aspect. 

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