Systemic inflammation enhances stimulant-induced striatal dopamine elevation

Abstract

Changes in the mesolimbic dopamine (DA) system are implicated in a range of neuropsychiatric conditions including addiction, depression and schizophrenia. Dysfunction of the neuroimmune system is often comorbid with such conditions and affects similar areas of the brain. The goal of this study was to use positron emission tomography with the dopamine D2 antagonist tracer, 11C-raclopride, to explore the effect of acute immune activation on striatal DA levels. DA transmission was modulated by an oral methylphenidate (MP) challenge in order to reliably elicit DA elevation. Elevation in DA concentration due to MP was estimated via change in 11C-raclopride binding potential from the baseline scan. Prior to the post-MP scan, subjects were pre-treated with either the immune activator lipopolysaccharide (LPS) or placebo (PBO) in a cross-over design. Immune activation was confirmed by measuring tumor necrosis factor alpha (TNFα), interleukin (IL)-6 and IL-8 concentration in plasma. Eight healthy subjects were scanned four times each to determine the MP-induced DA elevation under both LPS and PBO pre-treatment conditions. MP-induced DA elevation in the striatum was significantly greater (P<0.01) after LPS pre-treatment compared to PBO pre-treatment. Seven of eight subjects responded similarly. This effect was observed in the caudate and putamen (P<0.02), but was not present in ventral striatum. DA elevation induced by MP was significantly greater when subjects were pre-treated with LPS compared to PBO. The amplification of stimulant-induced DA signaling in the presence of systemic inflammation may have important implications for our understanding of addiction and other diseases of DA dysfunction.

Variation in chemokines plasma concentrations in primary care depressed patients associated with Internet-based cognitive-behavioral therapy

“…First is the demonstration that CBT-based interventions can normalize or even reduce the elevation of chemokines found in depressive patients. Because systemic inflammation can affect ascending monoamine transmitters involved in emotions and emotional learning (i.e., reward associated), CBT intervention, by reducing inflammation (including chemokines), has a biological way to improve depression-associated symptomatology 38 . In this regard, both inflammation and chemokines have been demonstrated to affect the activity and release of dopamine and serotonin in humans and experimental animals 21 .…”

Cocaine self‐administration is increased after frontal traumatic brain injury and associated with neuroinflammation

“…Further, while dopamine and inflammatory hypotheses are often discussed as separate mechanisms underlying cognitive changes, there is emerging evidence for interactions between dopamine signaling and neuroinflammation. In particular, immune activation can potentiate dopamine responses in the striatum, but lead to reduced motivation due to a downregulation of dopaminergic signaling (Felger et al, 2013;Petrulli et al, 2017). The current study aimed to characterize cocaine self-administration in TBI, and determine whether changes in dopamine or neuroinflammation were associated with elevated drug-taking.…”

Evaluation of plasma cytokines in patients with cocaine use disorders in abstinence identifies transforming growth factor alpha (TGFα) as a potential biomarker of consumption and dual diagnosis

“…These alterations are also found in some plasma circulating chemokines and cytokines ( Araos et al, 2015 ), indicating that alterations in pro- and anti-inflammatory factors may serve as potential biomarkers of an inflammatory state in the central nervous system (CNS). In fact, this systemic inflammation has been recently proposed to be a mechanism that facilitates dopamine signaling in the brain, which contributes to the addiction cycle ( Petrulli et al, 2017 ).…”