Social stress during adolescence activates long-term microglia inflammation insult in reward processing nuclei

• Published in: PloS one Vol. 13; no. 10; p. e0206421
• Main Authors: Rodríguez-Arias, Marta, Montagud-Romero, Sandra, Guardia Carrión, Ana María, Ferrer-Pérez, Carmen, Pérez-Villalba, Ana, Marco, Eva, López Gallardo, Meritxell, Viveros, María-Paz, Miñarro, José
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.10.2018; Public Library of Science (PLoS)
• Subjects: Addictions; Addictive behaviors; Adolescence; Adolescents; Animals; Astrocytes; Astrocytes - drug effects; Astrocytes - pathology; Behavior; Biology and Life Sciences; Brain; Brain - drug effects; Brain - pathology; Brain research; Cell Count; Child development; Cocaine; Cocaine - pharmacology; Conditioning; Conditioning (Psychology) - drug effects; Cytokines; Drug abuse; Drug self-administration; Inflammation; Inflammation - psychology; Long-term effects; Male; Medicine and Health Sciences; Metabolites; Mice; Microglia; Microglia - drug effects; Microglia - pathology; Neurobiology; Neuronal-glial interactions; Neurons - drug effects; Neurons - pathology; Neurophysiology; Neurosciences; Neurotoxicity; Nucleus accumbens; Physical Sciences; Physiology; Psychobiology; Psychological aspects; Psychology; Reinforcement; Reward; Rodents; Social interactions; Social Sciences; Stress; Stress, Psychological - pathology; Stress, Psychological - psychology; Stresses; Synaptic density; Teenagers; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0206421

The experience of social stress during adolescence is associated with higher vulnerability to drug use. Increases in the acquisition of cocaine self-administration, in the escalation of cocaine-seeking behavior, and in the conditioned rewarding effects of cocaine have been observed in rodents exposed to repeated social defeat (RSD). In addition, prolonged or severe stress induces a proinflammatory state with microglial activation and increased cytokine production. The aim of the present work was to describe the long-term effects induced by RSD during adolescence on the neuroinflammatory response and synaptic structure by evaluating different glial and neuronal markers. In addition to an increase in the conditioned rewarding effects of cocaine, our results showed that RSD in adolescence produced inflammatory reactivity in microglia that is prolonged into adulthood, affecting astrocytes and neurons of two reward-processing areas of the brain (the prelimbic cortex, and the nucleus accumbens core). Considered as a whole these results suggest that social stress experience modulates vulnerability to suffer a loss of glia-supporting functions and neuronal functional synaptic density due to drug consumption in later life.