Receptors noradrenergic

It has been suggested that modafinil increases wakefulness by activating ai noradrenergic receptors or hypothalamic cells that contain the peptide hypocre-tin [3], or that it may act by modulating the GABAergic tone that might lead to an increased dopamine release in the nucleus accumbens. On the other hand, modafinil does not have any effect in DAT knockout mice. 

Cornil C. A., Balthazart J., Motte P., Massotte L., Seutin V. (2002). Dopamine activates noradrenergic receptors in the preoptic area. J. Neurosci. 22(21), 9320-30. 

Aoki, C.,Venkatesan, C., Go, C. G., Forman, R. and Kurose, H. Cellular and subcellular sites for noradrenergic action in the monkey dorsolateral prefrontal cortex as revealed by the immunocytochemical localization of noradrenergic receptors and axons. Cereb. Cortex 8 269-277,1998. 

Capuano CA, Leibowitz SF, Barr GA. 1992. The pharmaco-ontogeny of the paraventricular alpha 2-noradrenergic receptor system mediating norepinephrine-induced feeding in the rat. Brain Res Dev Brain Res 68(1) 67-74. 

Dextroamphetamine is a powerful stimulant of the nervous system that manifests its effects by releasing dopamine and norepinephrine from presynaptic nerve endings, thus stimulating central dopaminergic and noradrenergic receptors. In certain doses it strengthens the excitatory process in the CNS, reduces fatigue, elevates mood and the capacity to work, reduces the need for sleep, and decreases appetite. 

Norepinephrine is released into the synapse from vesicles [(1) in Fig. 2.7] amphetamine facilitates this release. Norepinephrine acts in the CNS at two different types of noradrenergic receptors, the a and the P [see (2a), (2b) and (3) in Fig. 2.7]. a-Adrenergic receptors can be subdivided into receptors (coupled to phospholipase and located postsynaptically) and tt2 receptors (coupled to Gj and located primarily presynapti-cally) (Insel, 1996). P-Adrenergic receptors in the CNS are predominantly of the P subtype (3 in Fig. 2.7). P receptors are coupled to and lead to an increase in cAMP. Cyclic AMP triggers a variety of events mediated by protein kinases, including phosphorylation of the P receptor itself and regulation of gene expression via phosphorylation of transcription factors. 

Improve Inhibitory control of behavior and attention in both the cognitive and affective realms by optimizing neurochemical influences in prefrontal cortex via alpha-2A noradrenergic receptors (stimulants,... 

Enhance attentional resources in parietal or inferior temporal cortex via beta and alpha-1 noradrenergic receptors (stimulants,tamoxetine) and dopaminergic receptors (stimulants)... 

Biegon A, Reches A, Snyder L, etal Serotonergic and noradrenergic receptors in the rat brain modulation by chronic exposure to ovarian hormones. Life Sci 32 2015-2021, 1983... 

Dihydroxytryptamine lesions of the serotonin nuclei are known to attenuate the reduction in b-noradrenergic receptor binding induced by chronic tricyclic treatment (61). 

Preliminary results from case reports, case series, and open and increasingly better controlled trials have found TMS to be effective in the treatment of depression. TMS, antidepressants, and ECS appear to induce similar effects in animal behavioral models of depression and changes in brain neurochemical activity. These include changes in the forced swim test, increase in seizure threshold, and effects on b-noradrenergic receptor downregulation. Whereas seizures appear unnecessary to achieve clinical benefit with TMS, it is still unclear what aspects are beneficial. As noted earlier, although this modality is associated with some complications (e.g., headaches and, rarely, inadvertent seizure) relative to ECT and perhaps even pharmacotherapy under certain situations, it appears to be quite safe. Future studies of major depression should explore TMS-related issues such as the following ... 

Lithium blocks the release of thyroid hormones, which are known to potentiate b-noradrenergic receptor sensitivity. This has led to the speculation that excessive thyroid activity may contribute to an episode of mania in susceptible patients, and that the antimanic effect of lithium is, at least in part, due to its antithyroid action (26). In this context, CBZ can also decrease various thyroid indices. 

Although the density of fibers innervating various sites differs considerably, most regions of the CNS receive diffuse noradrenergic input. All noradrenergic receptor subtypes are metabotropic. When applied to neurons, norepinephrine can hyperpolarize them by increasing potassium conductance. This effect is mediated by ct2 receptors and has been characterized... 

On the other hand, alpha 2 receptors are the only presynaptic noradrenergic receptors on noradrenergic neurons. They regulate NE release and so are called autoreceptors. Presynaptic alpha 2 autoreceptors are located both on the axon terminal,... 

In terms of antidepressant actions, evidence points to the projection of noradrenergic neurons from the locus coeruleus to the frontal cortex as the substrate of this therapeutic action (Fig. 5-24). The noradrenergic receptor subtype that may mediate norepinephrine s antidepressant actions there is the beta 1 postsynaptic receptor. Therapeutic actions in cognition are not yet established but could theoretically be mediated by norepinephrine s pathway from the locus coeruleus to other areas of the frontal cortex (Fig. 5-25). Postsynaptic receptors thought to mediate cognitive actions of norepinephrine in animal models are especially the alpha 2 noradrenergic... 

Overactivity of noradrenergic neurons creates too much postsynaptic norepinephrine at noradrenergic receptors, particularly beta receptors (Fig. 8-14). As is consistent with the hypothesis of a state of norepinephrine excess in anxiety, it is possible to reduce symptoms of anxiety in some cases by blocking beta receptors with beta... 

Brain noradrenergic receptors in major depression and schizophrenia. Neuropsychopharmacology 21 69-81. 

Figure 8 Simplified diagram of a signaling cascade that involves NE, BDNF, and CREB after NE acts on the postsynaptic fi-noradrenergic receptor. NE couples to a G protein (Gas), which stimulates the production of cAMP from adenosine triphosphate (ATP). This reaction is catalyzed by adenylate cyclase (AC). cAMP activates protein kinase A (PKA). Inside the cell, PKA phosphorylates (P) the CREB protein, which binds upstream from specific regions of genes and regulates their expression. BDNF is one target of cAMP signaling pathways in the brain. CRE, cyclic AMP regulatory element ER, endoplasmic reticulum, [reprinted from Reference 76 with permission of the author and the publisher, Canadian Medical Association].

---