Effects on Monoamine Neurotransmitters

In laboratory animals, the acute intracerebral administration of IL-1 produces a rapid and significant increase in norepinephrine and serotonin (5-HT) turnover in several brain regions (Linthorst et al. 1995a, 1995b). Far less is known about the effect of chronic proinflammatory cytokine exposure on functioning of monoamine systems in either animals or humans; however, cytokines, including IFN-k, have been shown to diminish 5-HT availability as a result of a cytokine-mediated enhancement in the activity of indoleamine 2,3-dioxygenase (IDO), an enzyme that shunts tryptophan metabolism away from 5-HT toward kynurenine and quinolinic acid, which is known to have neurotoxic properties (Dantzer et al. 2007; Raison et al. 2006). Tryptophan is the primary precursor of 5-HT, and depletion of tryptophan has been associated with the precipitation of mood disturbances in vulnerable patients (Moore et al. 2000). Moreover, significant evidence suggests that serotonergic neurotransmission is decreased in many patients with depression (Owens and Nemeroff 1998). It has also been shown that proinflammatory cytokines, via p38 mitogen-activated protein kinase (MAPK)-linked pathways, can increase the expression and function of synaptic reuptake pumps for serotonin (and norepinephrine), potentially further contributing to reduced synaptic availability of mood-relevant monoamines (Zhu et al. 2005, 2006). Of interest, the development of major depression in the context of chronic IFN-s treatment has been shown to correlate closely with decreased plasma concentrations of tryptophan, possibly as a result of increased IDO activity, consistent with the idea that cytokine-induced decrements in 5-HT availability may contribute to the development of depression (Capuron et al. 2002b). Furthermore, treatment with paroxetine attenuates the behavioral consequences of IFN-ff, -mediated tryptophan depletion (Capuron et al. 2003a). In addition to the effects of chronic cytokine exposure on serotonergic transmission, both IL-2 and I FN-a, when they are administered chronically, have been reported to alter dopamine metabolism, and as noted above, IFN-a has been shown to lead to altered metabolic activity in brain regions high in dopaminergic neurocircuits including the basal ganglia (Capuron et al. 2007; Lacosta et al. 2000; Shuto et al. 1997).

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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