Norepinephrine locus coeruleus

Monoaminergic. AD also affects the ascending monoaminergic brainstem systems, including dopamine (ventral tegmental area), norepinephrine (locus coeruleus), and serotonin (raphe nuclei), which parallel the central choliner-... 

Ethanol also reduces the activity of the noradrenergic system in the locus coeruleus, and alterations in norepinephrine activity may account for some aspects of intoxication and the abstinence syndrome. The 0.2 antagonist clon-idine and the P-receptor antagonist propranolol reduce some symptoms of alcohol withdrawal (Bailly et al. 1992 Carlsson and Fasth 1976 Dobrydnjov et al. 2004 Kahkonen 2003 Petty et al. 1997 Wong et al. 2003). 

Redmond, DE and Huang, YH (1979) New evidence for a locus coeruleus-norepinephrine connection with anxiety. Life Sci. 25 2149-2162. 

Szot, R, Ashliegh, E. A., Kohen, R. etal. (1993). Norepinephrine transporter mRNA is elevated in the locus coeruleus following short- and long-term desipramine treatment. Brain Res., 618, 308-12. 

Noradrenaline (norepinephrine) brainstem locus coeruleus neurons... 

Pieribone, V. A., Xu, Z. Q., Zhang, X. et al. (1995). Galanin induces a hyperpolarization of norepinephrine-containing locus coeruleus neurons in the brainstem slice. Neuroscience 64, 861-74. 

Aston-Jones, G. Bloom, F. E. (1981). Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J. Neurosci. 1, 876-86. 

Basheer, R Magner, M., McCarley, R. W. Shiromani, P. J. (1998). REM sleep deprivation increases the levels of tyrosine hydroxylase and norepinephrine transporter mRNA in the locus coeruleus. Brain Res. Mol. Brain Res. 57,... 

Kodama, T. Koyama, Y. (2006). Nitric oxide from the laterodorsal tegmental neurons its possible retrograde modulation on norepinephrine release from the axon terminal of the locus coeruleus neurons. Neuroscience 138, 245-56. 

Nicotine causes a release of norepinephrine from the locus coeruleus and facilitates release of norepinephrine in the hippocampus (Gallardo and Leslie 1998 Mitchell 1993 Sershen etal. 1997 Fu et al. 1999). The norepinephrine released by nicotine, in turn, modulates raphe neurons (Li et al. 1998). 

Lobeline also increases basal release of norepinephrine, but norepinephrine release may be reduced at higher lobeline concentrations (Rao et al. 1997). Unlike acetylcholine, lobeline does not reduce the release of dopamine or norepinephrine by NMDA receptors, but it does block nicotine-induced release of norepinephrine from the locus coeruleus (Gallardo and Leslie 1998). Lobeline also evokes release of serotonin, which is mediated by uptake transporters and unaffected by mecamylamine (Lendvai et al. 1996). 

Agonist/antagonist effects on serotonin receptors Time-dependent increases/decreases on dopamine and norepinephrine Age-dependent effects on MAO Increased firing of locus coeruleus neurons... 

Gallardo KA, Leslie FM. (1998). Nicotine-stimulated release of [3FI]norepinephrine from fetal rat locus coeruleus cells in culture. J Neurochem. 70(2) 663-70. 

Norepinephrine is released into the brain by a few pathways that originate in the brain stem and one pathway in another part of the brain called the pons. The pathway in the pons, called the locus coeruleus, is particularly important... 

Norepinephrine is made in cells located in the brain stem, mostly in a group of cells called the locus coeruleus. These neurons send widespread projections throughout the brain. This distribution has functional consequences. Small disturbances in the locus coeruleus can have a large impact on many different brain areas at the same time, and thus influence many behaviors. Disorders of emotion and mood are similar in that they simultaneously impact many different behaviors. Therefore, it is reasonable to suggest that norepinephrine might affect emotion in some ways. 

Noradrenergic neuromodulatory system. The neurons that synthesize norepinephrine (molecular structure in box) are located in several brainstem nuclei including the nucleus locus coeruleus, from which axons extend caudally (to the spinal cord), locally (to the brainstem and cerebellum), and rostrally (to the thalamus, subthalamus, limbic system, and to the cerebral cortex). Compare with figure 2.1 to identify structures shown. 

In addition to the cholinergic and glutaminergic reticular neurons already described as ebbing and flowing in concert with the rest of the centrencephalic core, the brain stem also contains the important aminergic nuclei, the locus coeruleus (secreting norepinephrine) and the raphe... 

Hess s model is all the more prescient because, at the time of its articulation, the cellular and molecular neurobiology of the central instantiation of the two branches of the autonomic nervous system were completely unknown. He had to infer their existence from his knowledge of the peripheral system and from the effects of his manipulation of the brain upon their outflow. The breakthrough came only in the early 1960s, when Anica Dahlstrom, K]ell Euxe, and others identified the norepinephrine containing cells of the locus coeruleus and the serotonin containing cells of the midline raphe nucleus. And it was even later when Marcel Mesulam and others mapped the central cholinergic neuronal system. 

The first observation was the more unexpected because we were under the mistaken impression that the locus coeruleus should turn on, not off, in REM. But once we realized that we had the role of norepinephrine backwards, it was not difficult to find other REM-off cells—not only in the locus coeruleus, but also in the raphe nuclei—and to see that both of the pontine aminergic neuromodulators supported waking just as any extension of Hess s principles would suggest. Even the central sympathetic system works toward ergotrophic ends. Eor sleep to occur, this system must first be deactivated to allow NREM sleep to develop, and then actively suppressed, to allow REM to develop. 

But the fact that we experience anxiety—often of panic proportions in our REM sleep dreams when the locus coeruleus is shut down completely—means two things that arousal—at least in the waking sense of the term—and anxiety are completely dissociable and that the brain-mind is capable of generating anxiety without the help of the locus coeruleus In fact, REM sleep dream anxiety cannot depend upon norepinephrine, or serotonin, or histamine either, which leaves dopamine and acetylcholine as the only two neuromodulatory candidates for... 

There are many specific noradrenergic pathways in the brain, each mediating a different physiological function. For example, one projection from the locus coeruleus to frontal cortex is thought to be responsible for the regulatory actions of NE on mood (Fig. 5—24) another projection to prefrontal cortex mediates the effects of NE on attention (Fig. 5—25). Different receptors may mediate these differential effects of norepinephrine in frontal cortex, postsynaptic beta 1 receptors for mood (Fig. 5—24) and postsynaptic alpha 2 for attention and cognition (Fig. 5—25). 

The projection from the locus coeruleus to limbic cortex may regulate emotions, as well as energy, fatigue, and psychomotor agitation or psychomotor retardation (Fig. 5—26). A projection to the cerebellum may regulate motor movements, especially tremor (Fig. 5—27). Brainstem norepinephrine in cardiovascular centers controls blood pressure (Fig. 5—28). Norepinephrine from sympathetic neurons leaving the spinal cord to innervate peripheral tissues control heart rate (Fig. 5—29) and bladder emptying (Fig. 5—30). 

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