TY  - JOUR
PY  - 2018//
TI  - From traumatic childhood to cocaine abuse: the critical function of the immune system
JO  - Biological psychiatry
A1  - Lo Iacono, Luisa
A1  - Catale, Clarissa
A1  - Martini, Alessandro
A1  - Valzania, Alessandro
A1  - Viscomi, Maria Teresa
A1  - Chiurchiù, Valerio
A1  - Guatteo, Ezia
A1  - Bussone, Silvia
A1  - Perrone, Fabiana
A1  - Di Sabato, Paola
A1  - Aricò, Eleonora
A1  - D'Argenio, Alberto
A1  - Troisi, Alfonso
A1  - Mercuri, Nicola B.
A1  - Maccarrone, Mauro
A1  - Puglisi-Allegra, Stefano
A1  - Casella, Pietro
A1  - Carola, Valeria
SP  - 905
EP  - 916
VL  - 84
IS  - 12
N2  - BACKGROUND: Experiencing traumatic childhood is a risk factor for developing substance use disorder, but the mechanisms that underlie this relationship have not been determined. Adverse childhood experiences affect the immune system, and the immune system mediates the effects of psychostimulants. However, whether this system is involved in the etiology of substance use disorder in individuals who have experienced early life stress is unknown. <br><br>METHODS: In this study, we performed a series of ex vivo and in vivo experiments in mice and humans to define the function of the immune system in the early life stress-induced susceptibility to the neurobehavioral effects of cocaine. <br><br>RESULTS: We provide evidence that exposure to social stress at an early age permanently sensitizes the peripheral (splenocytes) and brain (microglia) immune responses to cocaine in mice. In the brain, microglial activation in the ventral tegmental area of social-stress mice was associated with functional alterations in dopaminergic neurotransmission, as measured by whole-cell voltage clamp recordings in dopamine neurons. Notably, preventing immune activation during the social-stress exposure reverted the effects of dopamine in the ventral tegmental area and the cocaine-induced behavioral phenotype to control levels. In humans, cocaine modulated toll-like receptor 4-mediated innate immunity, an effect that was enhanced in those addicted to cocaine who had experienced a difficult childhood. <br><br>CONCLUSIONS: Collectively, our findings demonstrate that sensitization to cocaine in early life-stressed individuals involves brain and peripheral immune responses and that this mechanism is shared between mice and humans.<br><br>Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.<p />  <p>Language: en</p>
LA  - en
SN  - 0006-3223
UR  - http://dx.doi.org/10.1016/j.biopsych.2018.05.022
ID  - ref1
ER  -