Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood

NEUROPHARMACOLOGY

卷:144

Article

Saravia, Rocio¹  Ten-Blanco, Marc^1,6  Julia-Hernandez, Marina¹  Gagliano, Humberto^2,3,4  Andero, Raul^2,3,4,5  Armario, Antonio^2,3,4  Maldonado, Rafael¹  Berrendero, Fernando^1,6 

[1] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Neuropharmacol Lab, PRBB, Barcelona 08003, Spain

[2] Univ Autonoma Barcelona, Inst Neurosci, E-08193 Barcelona, Spain

[3] Univ Autonoma Barcelona, Sch Biosci, Anim Physiol Unit, E-08193 Barcelona, Spain

[4] Corp Sanitaria Parc Tauli, CIBERSAM, Sabadell, Spain

[5] Univ Autonoma Barcelona, Dept Psychobiol & Methodol Hlth Sci, Bellaterra, Spain

[6] Univ Francisco Vitoria, Fac Expt Sci, Madrid 28223, Spain

关键词: Delta(9)-tetrahydrocannabinol;    Stress;    Adolescence;    Fear extinction;    Dendritic spines;    Amygdala;   

DOI  :  10.1016/j.neuropharm.2018.11.016

来源: Elsevier

【 摘 要 】

Delta(9)-tetrahydrocannabinol (THC) consumption during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. The interaction between genetic or environmental events and cannabinoid exposure in the adolescent period can also contribute to exacerbate behavioural deficits in adulthood. Here we investigate the effects of THC treatment as well as the consequences of concomitant THC and stress exposure during adolescence in the extinction of fear memory in adult mice. Adolescent mice treated with THC and exposed to stress exhibit impaired cued fear extinction in adulthood. However, no effect was observed in animals exposed to these two factors separately. Notably, resistance to fear extinction was associated with decreased neuronal activity in the basolateral amygdala (BLA) and the infralimbic prefrontal cortex, suggesting a long-term dysregulation of the fear circuit. These changes in neuronal activation were paralleled with structural plasticity alterations. Indeed, an increase of immature dendritic spines in pyramidal neurons of the BLA was revealed in mice simultaneously exposed to THC and stress. Corticosterone levels were also enhanced after the cued fear conditioning session in the same experimental group. These results show that an interaction between cannabis exposure and stress during adolescence may lead to long-term anxiety disorders characterized by the presence of pathological fear.

【 授权许可】

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