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Neuropharmacology. 2019 Jan;144:345-357. doi: 10.1016/j.neuropharm.2018.11.016. Epub 2018 Nov 12.

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

Author information

1
Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, PRBB, 08003, Barcelona, Spain.
2
Institute of Neuroscience and Animal Physiology Unit (School of Biosciences), Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Barcelona, Spain; CIBERSAM, Corporació Sanitaria Parc Taulí, Sabadell, Spain.
3
Institute of Neuroscience and Animal Physiology Unit (School of Biosciences), Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Barcelona, Spain; CIBERSAM, Corporació Sanitaria Parc Taulí, Sabadell, Spain; Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona, Bellaterra, Spain.
4
Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, PRBB, 08003, Barcelona, Spain. Electronic address: rafael.maldonado@upf.edu.
5
Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, PRBB, 08003, Barcelona, Spain; Faculty of Experimental Sciences, Universidad Francisco de Vitoria, UFV, 28223, Pozuelo de Alarcón, Madrid, Spain. Electronic address: fernando.berrendero@ufv.es.

Abstract

Δ9-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.

KEYWORDS:

Adolescence; Amygdala; Dendritic spines; Fear extinction; Stress; Δ(9)-tetrahydrocannabinol

[Indexed for MEDLINE]

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