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Higuera Matas, Alejandro

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0000-0003-3438-9387
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Higuera Matas
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  • Publicación
    The long-term effects of adolescent Δ9-tetrahydrocannabinol on brain structure and function assessed through neuroimaging techniques in male and female rats
    (Elsevier, 2023-06-03) Orihuel Menéndez, Javier; Capellán, Roberto; Casquero Veiga, Marta; Soto Montenegro, María Luisa; Desco, Manuel; Oteo Vives, Marta; Ibáñez Moragues, Marta; Magro Calvo, Natalia; Luján, Víctor M.; Morcillo, Miguel Ángel; Ambrosio Flores, Emilio; Higuera Matas, Alejandro; https://orcid.org/0000-0001-9586-0684; https://orcid.org/0000-0003-0306-7916
    Several studies performed on human subjects have examined the effects of adolescent cannabis consumption on brain structure or function using brain imaging techniques. However, the evidence from these studies is usually heterogenous and affected by several confounding variables. Animal models of adolescent cannabinoid exposure may help to overcome these difficulties. In this exploratory study, we aim to increase our understanding of the protracted effects of adolescent Δ9-tetrahydrocannabinol (THC) in rats of both sexes using magnetic resonance (MR) to obtain volumetric data, assess grey and white matter microstructure with diffusion tensor imaging (DTI) and measure brain metabolites with 1H-MR spectroscopy (MRS); in addition, we studied brain function using positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-glucose as the tracer. THC-exposed rats exhibited volumetric and microstructural alterations in the striatum, globus pallidus, lateral ventricles, thalamus, and septal nuclei in a sex-specific manner. THC administration also reduced fractional anisotropy in several white matter tracts, prominently in rostral sections, while in vivo MRS identified lower levels of cortical choline compounds. THC-treated males had increased metabolism in the cerebellum and olfactory bulb and decreased metabolism in the cingulate cortex. By contrast, THC-treated females showed hypermetabolism in a cluster of voxels comprising the entorhinal piriform cortices and in the cingulate cortex. These results indicate that mild THC exposure during adolescence leaves a lingering mark on brain structure and function in a sex-dependant manner. Some of the changes found here resemble those observed in human studies and highlight the importance of studying sex-specific effects in cannabinoid research.
  • Publicación
    Cocaine-induced Fos expression in the rat brain: Modulation by prior Δ9-tetrahydrocannabinol exposure during adolescence and sex-specific effects
    (Elsevier, 2021-04-24) Orihuel Menéndez, Javier; Gómez Rubio, Laura; Valverde, Claudia; Capellán, Roberto; Roura Martínez, David; Ucha Tortuero, Marcos; Ambrosio Flores, Emilio; Higuera Matas, Alejandro
    It has been suggested that cannabis consumption during adolescence may be an initial step to cocaine use in adulthood. Indeed, previous preclinical data show that adolescent exposure to cannabinoids (both natural and synthetic) potentiates cocaine self-administration in rats. Here we aimed at gaining a deeper understanding of the cellular activation patterns induced by cocaine as revealed by Fos imaging and how these patterns may change due to adolescent exposure to THC. Male and female Wistar rats were administered every other day THC (3 mg/kg i.p.) or vehicle from postnatal day 28–44. At adulthood (PND90) they were given an injection of cocaine (20 mg/kg i.p.) or saline and sacrificed 90 min later. Cocaine-induced Fos activation was measured by immunohistochemistry as an index of cellular activation. We found that cocaine-induced activation in the motor cortex was stronger in THC-exposed rats. Moreover, there was significant sex-dependent interaction between cocaine and adolescent THC exposure in the dorsal hypothalamus, suggesting that cocaine induced a more robust cellular activation in THC-exposed females but not in THC-treated males. Other THC- and cocaine-induced effects were also evident. These results add to the previous literature suggesting that the behavioral, cellular, molecular, and brain-activating actions of cocaine are modulated by early experience with cannabinoids and provide additional knowledge that may explain the enhanced actions of cocaine in rats exposed to cannabinoids during their adolescence.