Interaction between maternal immune activation and peripubertal stress in rats: impact on cocaine addiction-like behaviour, morphofunctional brain parameters and striatal transcriptome.

Autor: Capellán R; Department of Psychobiology, Faculty of Psychology, UNED, Madrid, Spain., Orihuel J; Department of Psychobiology, Faculty of Psychology, UNED, Madrid, Spain., Marcos A; Department of Psychobiology, Faculty of Psychology, UNED, Madrid, Spain., Ucha M; Department of Psychobiology, Faculty of Psychology, UNED, Madrid, Spain., Moreno-Fernández M; Department of Psychobiology, Faculty of Psychology, UNED, Madrid, Spain., Casquero-Veiga M; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain.; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain., Soto-Montenegro ML; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.; Grupo de Fisiopatología y Farmacología del Sistema Digestivo de la Universidad Rey Juan Carlos (NEUGUT), Madrid, Spain.; CIBER de Salud Mental (CIBERSAM), Madrid, Spain., Desco M; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.; CIBER de Salud Mental (CIBERSAM), Madrid, Spain.; Departamento de Bioingeniería, Universidad Carlos III de Madrid, Madrid, Spain., Oteo-Vives M; CIEMAT - Research Centre for Energy, Environment and Technology, Medical Applications of Ionizing Radiation Unit, Madrid, Spain., Ibáñez-Moragues M; CIEMAT - Research Centre for Energy, Environment and Technology, Medical Applications of Ionizing Radiation Unit, Madrid, Spain., Magro-Calvo N; CIEMAT - Research Centre for Energy, Environment and Technology, Medical Applications of Ionizing Radiation Unit, Madrid, Spain., Morcillo MÁ; CIEMAT - Research Centre for Energy, Environment and Technology, Medical Applications of Ionizing Radiation Unit, Madrid, Spain., Ambrosio E; Department of Psychobiology, Faculty of Psychology, UNED, Madrid, Spain. eambrosio@psi.uned.es., Higuera-Matas A; Department of Psychobiology, Faculty of Psychology, UNED, Madrid, Spain. ahiguera@psi.uned.es.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2023 Mar 08; Vol. 13 (1), pp. 84. Date of Electronic Publication: 2023 Mar 08.
DOI: 10.1038/s41398-023-02378-6
Abstrakt: Substance use disorders are more prevalent in schizophrenia, but the causal links between both conditions remain unclear. Maternal immune activation (MIA) is associated with schizophrenia which may be triggered by stressful experiences during adolescence. Therefore, we used a double-hit rat model, combining MIA and peripubertal stress (PUS), to study cocaine addiction and the underlying neurobehavioural alterations. We injected lipopolysaccharide or saline on gestational days 15 and 16 to Sprague-Dawley dams. Their male offspring underwent five episodes of unpredictable stress every other day from postnatal day 28 to 38. When animals reached adulthood, we studied cocaine addiction-like behaviour, impulsivity, Pavlovian and instrumental conditioning, and several aspects of brain structure and function by MRI, PET and RNAseq. MIA facilitated the acquisition of cocaine self-administration and increased the motivation for the drug; however, PUS reduced cocaine intake, an effect that was reversed in MIA + PUS rats. We found concomitant brain alterations: MIA + PUS altered the structure and function of the dorsal striatum, increasing its volume and interfering with glutamatergic dynamics (PUS decreased the levels of NAA + NAAG but only in LPS animals) and modulated specific genes that could account for the restoration of cocaine intake such as the pentraxin family. On its own, PUS reduced hippocampal volume and hyperactivated the dorsal subiculum, also having a profound effect on the dorsal striatal transcriptome. However, these effects were obliterated when PUS occurred in animals with MIA experience. Our results describe an unprecedented interplay between MIA and stress on neurodevelopment and the susceptibility to cocaine addiction.
(© 2023. The Author(s).)
Databáze: MEDLINE
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