Sex- and age-specific respiratory alterations induced by prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 in rats

dc.contributor.authorPatrone, Luis Gustavo A. [UNESP]
dc.contributor.authorFerrari, Gustavo D.
dc.contributor.authorda Silva, Rodrigo Moreira
dc.contributor.authorAlberici, Luciane C.
dc.contributor.authorLopes, Norberto Peporine
dc.contributor.authorStabile, Angelita M.
dc.contributor.authorKlein, Wilfried
dc.contributor.authorBícego, Kênia C. [UNESP]
dc.contributor.authorGargaglioni, Luciane H. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2023-07-29T13:42:55Z
dc.date.available2023-07-29T13:42:55Z
dc.date.issued2023-07-01
dc.description.abstractBackground and Purpose: Cannabis legalization has risen in many countries, and its use during pregnancy has increased. The endocannabinoid system is present in the CNS at early stages of embryonic development, and regulates functional brain maturation including areas responsible for respiratory control, data on the influence of external cannabinoids on the development of the respiratory system and possible consequences during postnatal life are limited. Experimental Approach: We evaluated the effects of prenatal exposure to synthetic cannabinoid (WIN 55,212-2 [WIN], 0.5 mg·kg−1·day−1) on the respiratory control system in neonatal (P0, P6–7 and P12–13) and juvenile (P27–28) male and female rats. Key Results: WIN administration to pregnant rats interfered sex-specifically with breathing regulation of offspring, promoting a greater sensitivity to CO2 at all ages in males (except P6–7) and in juvenile females. An altered hypoxic chemoreflex was observed in P0 (hyperventilation) and P6–7 (hypoventilation) males, which was absent in females. Along with breathing alterations, brainstem analysis showed an increase in the number of catecholaminergic neurons and cannabinoid receptor type 1 (CB1) and changes in tissue respiration in the early males. A reduction in pulmonary compliance was observed in juvenile male rats. Preexposure to WIN enhanced spontaneous apnoea and reduced the number of serotoninergic (5-HT) neurons in the raphe magnus nucleus of P0 females. Conclusions and Implications: These data demonstrate that excess stimulation of the endocannabinoid system during gestation has prolonged and sex-specific consequences for the respiratory control system.en
dc.description.affiliationDepartment of Animal Morphology and Physiology São Paulo State University – UNESP/FCAV, São Paulo
dc.description.affiliationDepartment of Biomolecular Sciences School of Pharmaceutical Sciences of Ribeirão Preto University of São Paulo, São Paulo
dc.description.affiliationDepartment of General and Specialized Nursing School of Nursing of Ribeirão Preto University of São Paulo, São Paulo
dc.description.affiliationDepartment of Biology School of Philosophy Sciences and Literature of Ribeirão Preto University of São Paulo, São Paulo
dc.description.affiliationUnespDepartment of Animal Morphology and Physiology São Paulo State University – UNESP/FCAV, São Paulo
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdFAPESP: 2016/17681-9
dc.description.sponsorshipIdFAPESP: 2017/05318-0
dc.description.sponsorshipIdFAPESP: 2020/01702-2
dc.description.sponsorshipIdCNPq: 303802/2018-9
dc.description.sponsorshipIdCNPq: 308249/2019-4
dc.description.sponsorshipIdCNPq: 407490/2018-3
dc.description.sponsorshipIdCAPES: 88887.194785/2018-00
dc.description.sponsorshipIdCAPES: Finance Code 001
dc.description.sponsorshipIdCAPES: Process: 88887.1947
dc.format.extent1766-1789
dc.identifierhttp://dx.doi.org/10.1111/bph.16044
dc.identifier.citationBritish Journal of Pharmacology, v. 180, n. 13, p. 1766-1789, 2023.
dc.identifier.doi10.1111/bph.16044
dc.identifier.issn1476-5381
dc.identifier.issn0007-1188
dc.identifier.scopus2-s2.0-85148507363
dc.identifier.urihttp://hdl.handle.net/11449/248395
dc.language.isoeng
dc.relation.ispartofBritish Journal of Pharmacology
dc.sourceScopus
dc.subjectbrainstem
dc.subjectCB1/CB2 receptor
dc.subjectchemosensitivity
dc.subjectdevelopment
dc.subjectWIN 55,212-2
dc.titleSex- and age-specific respiratory alterations induced by prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 in ratsen
dc.typeArtigo

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