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1.
Brain Behav Immun ; 119: 301-316, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38608740

RESUMO

Maternal obesity is associated with an increased risk of psychiatric disorders such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While numerous studies focus on preventive measures targeting the mothers, only a limited number provide practical approaches for addressing the damages once they are already established. We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on hypothalamic inflammation and metabolic disturbances, however, little is known about this relationship on behavioral manifestations and neurochemical imbalances in other brain regions. Therefore, here we tested whether CBD treatment could mitigate anxiety-like and social behavioral alterations, as well as neurochemical disruptions in both male and female offspring of obese dams. Female Wistar rats were fed a cafeteria diet for 12 weeks prior to mating, and during gestation and lactation. Offspring received CBD (50 mg/kg) from weaning for 3 weeks. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and neurochemical markers were evaluated in the prefrontal cortex (PFC) and hippocampus. CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, followed by rescuing effects on imbalanced neurotransmitter and endocannabinoid concentrations and altered expression of glial markers, CB1, oxytocin and dopamine receptors, with important differences between sexes. Overall, the findings of this study provide insight into the signaling pathways for the therapeutic benefits of CBD on neuroinflammation and neurochemical imbalances caused by perinatal maternal obesity in the PFC and the hippocampus, which translates into the behavioral manifestations, highlighting the sexual dimorphism encompassing both the transgenerational effect of obesity and the endocannabinoid system.


Assuntos
Ansiedade , Comportamento Animal , Canabidiol , Hipocampo , Obesidade Materna , Córtex Pré-Frontal , Efeitos Tardios da Exposição Pré-Natal , Ratos Wistar , Animais , Feminino , Canabidiol/farmacologia , Gravidez , Ratos , Masculino , Obesidade Materna/metabolismo , Ansiedade/metabolismo , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Comportamento Social , Obesidade/metabolismo , Endocanabinoides/metabolismo
2.
Behav Brain Res ; 372: 112055, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31233821

RESUMO

Extinction is the learned inhibition of retrieval. It is the mainstay of exposure therapy, which is widely used to treat drug addiction, phobias and fear-related pathologies such as post-traumatic stress disorder. The serotonin (5-HT) system is positioned to modulate the extinction circuitry via ascending 5-HT projections that innervate certain brain structures including the hippocampus and the basolateral amygdala (BLA). The most recently described serotoninergic receptors 5-HT5A, 5-HT6, 5-HT7 affect different memory processes and so are putative therapeutic targets for disorders related to cognition; however, their role in the extinction of contextual fear conditioning (CFC) has not been studied yet. Here we investigate the role of these receptors in the CA1 region of the hippocampus and the BLA in the extinction of CFC. For this, male rats were implanted with cannulae in the CA1 or in the BLA region through which they received immediately or 3 h after extinction training of CFC infusions of SB699551 (10 µg/side), 5-HT5A antagonist; WAY-208466 (0.04 µg/side), 5-HT6 agonist; SB-271046A (10 µg/side), 5-HT6 antagonist; AS-19 (5 µg/side), 5-HT7 agonist; SB-269970 (5 µg/side), 5-HT7 antagonist. After 24 h, animals were submitted to a 3 min extinction test. Results show that the infusion immediately after extinction training of 5-HT5A, 5-HT6 and 5-HT7 antagonists, and 3 h after extinction training of 5-HT5A and 5-HT7 antagonists in the BLA region, but not in CA1, facilitates the extinction of CFC memory.


Assuntos
Extinção Psicológica/fisiologia , Medo/fisiologia , Receptores de Serotonina/fisiologia , Tonsila do Cerebelo/fisiologia , Animais , Complexo Nuclear Basolateral da Amígdala/fisiologia , Encéfalo/fisiologia , Condicionamento Clássico/fisiologia , Medo/psicologia , Hipocampo/fisiologia , Masculino , Memória/fisiologia , Ratos , Ratos Wistar , Receptores de Serotonina/metabolismo
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