2023-03-16 ミシガン大学
サイントラッカーは、薬物摂取の報酬効果が大きく、苦痛な結果があっても薬物を続けます。ゴールトラッカーは、結果に直面して薬物摂取をやめます。サイントラッカーは、機能不全のコリン輸送体が多くあり、注意力の制御が悪くなることが貢献しています。増加したサイトカイン産生と減少したコリン輸送体機能との重要な相互作用が注意力の制御障害および中毒性に対する脆弱性に貢献していることが示唆されています。
<関連情報>
- https://news.umich.edu/immune-signals-identified-in-the-brain-that-contribute-to-addiction-vulnerability/
- https://www.eneuro.org/content/10/3/ENEURO.0023-23.2023
アディクション脆弱性特性におけるコリン作動性シグナル伝達の神経免疫調節機構 Neuro-Immune Modulation of Cholinergic Signaling in an Addiction Vulnerability Trait
Hanna Carmon, Evan C. Haley, Vinay Parikh, Natalie C. Tronson and Martin Sarter
eNeuro Published:21 February 2023
DOI: https://doi.org/10.1523/ENEURO.0023-23.2023
Abstract
Sign-tracking (ST) describes the propensity to approach and contact a Pavlovian reward cue. By contrast, goal-trackers (GTs) respond to such a cue by retrieving the reward. These behaviors index the presence of opponent cognitive-motivational traits, with STs exhibiting attentional control deficits, behavior dominated by incentive motivational processes, and vulnerability for addictive drug taking. Attentional control deficits in STs were previously attributed to attenuated cholinergic signaling, resulting from deficient translocation of intracellular choline transporters (CHTs) into synaptosomal plasma membrane. Here, we investigated a posttranslational modification of CHTs, poly-ubiquitination, and tested the hypothesis that elevated cytokine signaling in STs contributes to CHT modification. We demonstrated that intracellular CHTs, but not plasma membrane CHTs, are highly ubiquitinated in male and female sign-tracking rats when compared with GTs. Moreover, levels of cytokines measured in cortex and striatum, but not spleen, were higher in STs than in GTs. Activation of the innate immune system by systemic administration of the bacterial endotoxin lipopolysaccharide (LPS) elevated ubiquitinated CHT levels in cortex and striatum of GTs only, suggesting ceiling effects in STs. In spleen, LPS increased levels of most cytokines in both phenotypes. In cortex, LPS particularly robustly increased levels of the chemokines CCL2 and CXCL10. Phenotype-specific increases were restricted to GTs, again suggesting ceiling effects in STs. These results indicate that interactions between elevated brain immune modulator signaling and CHT regulation are essential components of the neuronal underpinnings of the addiction vulnerability trait indexed by sign-tracking.
