Aminergic

The role of MAO in terminating the action of the aminergic neurotransmitters and dietary amines has... 

Acute treatment with nonselective MAO inhibitors (iproniazid, tranylcypromine, phenelzine), as a consequence of inhibiting both forms of the enzyme, increase, brain levels of all monoamines (phenylethylamine, tryptamine, methylhistamine aminergic neurotransmitters (dopamine, noradr enaline, adrenaline and serotonin). By contrast MAO-A inhibitors (clorgyline) increase serotonin and noradrenaline, while MAO-B inhibitors (selegiline, rasagiline) increase brain levels... 

Major efferent projections of the hypothalamic orexin system comprise descending and ascending, dorsal and ventral pathways that terminate preferentially in aminergic, endocrine, and autonomic control centers in the hypothalamus, midbrain, brainstem, and spinal cord, as well as in limbic cortical and subcortical structures, including sqDtum, amygdala, thalamus,... 

Histamine receptors were first divided into two subclasses Hi and H2 by Ash and Schild (1966) on the basis that the then known antihistamines did not inhibit histamine-induced gastric acid secretion. The justification for this subdivision was established some years later when Black (see Black et al. 1972) developed drugs, like cimetidine, that affected only the histamine stimulation of gastric acid secretion and had such a dramatic impact on the treatment of peptic ulcers. A recently developed H2 antagonist zolantidine is the first, however, to show significant brain penetration. A further H3 receptor has now been established. It is predominantly an autoreceptor on histamine nerves but is also found on the terminals of aminergic, cholinergic and peptide neurons. All three receptors are G-protein-coupled but little is known of the intracellular pathway linked to the H3 receptor and unlike Hi and H2 receptors it still remains to be cloned. Activation of Hi receptors stimulates IP3 formation while the H2 receptor is linked to activation of adenylate cyclase. 

It is important to emphasise that a lesion of the reticular system disrupts a number of afferent inputs to the cortex. Particularly important in this respect are the mono-aminergic (especially noradrenaline, 5-HT and histamine) and cholinergic pathways. When the ascending inputs from these neurons are destroyed, sleep is passive and not at all like natural sleep which, as detailed above, has distinct phases and depends on brainstem influences on cortical function. How these different neurotransmitters might influence sleep and arousal will be considered next. 

Schmidt, C.J. Levin, J.A. and Lovenberg, W. In vitro and in vivo neurochemical effects of methylenedioxymethamphetamine on striatal mono-aminergic systems in the rat brain. Biochem Pharmacol 36(5) 747-755, 1987. 

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).

Semba, K. (1993). Aminergic and cholinergic afferents to REM sleep induction regions of the pontine reticular formation in the rat. J. Comp. Neurol. 330, 543-56. 

Rates of firing of aminergic, cholinergic, and orexinergic neurons involved in the regulation of sleep and waking... 

Losier, B. J. Semba, K. (1993). Dual projections of single cholinergic and aminergic brainstem neurons to the thalamus and basal forebrain in the rat. Brain Res. 

Orexin neurons innervate all the major brain regions implicated in the generation of wakefulness including the aminergic and cholinergic brainstem... 

Kaslin J., Nystedt J. M., Ostergard M., Peitsaro N., Panula P. (2004). The orexin/ hypocretin system in zebrafish is connected to the aminergic and cholinergic systems. J. Neurosci. 24, 2678-89. 

Stanley, M., Traskman-Bendz, L. and Dorovini-Zis, K. Correlations between aminergic metabolites simultaneously obtained from human CSF and brain. Life Sciences 37 1279-1286,1985. 

Shi, L. and Javitch, J. A. (2002) The binding site of aminergic G protein-coupled receptors. Annu. Rev. Pharmacol. Toxicol. 42,437 467. 

Sastry, B. S. R., and Sinclair, J. G. (1976) Tonic inhibitory influence of a supraspinal mono-aminergic system on recurrent inhibition of extensor monosynaptic reflex. Brain Res., 117 69— 76. 

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