Title : Alcohol-exacerbates post-traumatic stress psychiatric behavior and its neuropathological sequalae in experimental mice: preventive effects of morin - Ben-Azu_2024_Alcohol__ |
Author(s) : Ben-Azu B , Toloyai PY , Adebesin A , Ojiokor VO , Adebayo OG , Fokoua AR , Moke GE , Ejukolemu EJ , Akpojevughe IO , Abdulkadir AM , Okwuchi E |
Ref : Alcohol , : , 2024 |
Abstract :
Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are very prevalent and co-occurring. It is unclear how alcohol exacerbates PTSD predicaments owing to less characterized pathophysiological mechanisms. Also, studies on pharmacological agents that can effectively reverse PTSD-AUD comorbidity have, to date, been scarce. Hence, we designed a methodological approach to investigate the pathophysiological mechanisms and pharmacological outcomes of morin, a neuroprotective flavonoid in mice. After 7 days of PTSD following single-prolonged stress (SPS) induction in mice, the PTSD mice were exposed to intermittent binge ethanol administration using ethanol (2g/kg, oral gavage) every other day, alongside daily morin (50 and 100mg/kg) or fluoxetine (10mg/kg) from days 8-21. The consequences of PTSD-AUD behavior, hypothalamic-pituitary-adrenal-axis (HPA-axis) dysfunction, neurochemistry, oxidative/nitrergic stress, and inflammation were evaluated in the prefrontal-cortex (PFC), striatum, and hippocampus of mice. The exacerbated anxiety-like behavior, and spatial/non-spatial memory deficits, with general depressive phenotypes and social stress susceptibility by SPS-ethanol interaction, were alleviated by morin and fluoxetine, evidenced by reduced corticosterone release and adrenal hypertrophy. SPS-ethanol exacerbates dopamine, serotonin, and glutamic acid decarboxylase alterations, and monoamine oxidase-B and acetylcholinesterase hyperactivities in the striatum, PFC, and hippocampus, respectively, which were prevented by morin. Compared to SPS-ethanol aggravation, morin prevented TNF-alpha, and IL-6 release, malondialdehyde and nitrite levels, with improved antioxidant (glutathione, superoxide-dismutase, catalase) levels in the hippocampus, PFC, and striatum. Overall, these findings suggest that AUD exacerbated PTSD might be primarily connected, among other mechanisms, with aggravated HPA-axis dysfunction, upregulated neurochemical degradative enzymes, enhancement of oxidative/nitrergic stress and neuroinflammation, stereo-selectively in the mice brains, which morin abated via the preventive mechanisms. |
PubMedSearch : Ben-Azu_2024_Alcohol__ |
PubMedID: 39094850 |
Ben-Azu B, Toloyai PY, Adebesin A, Ojiokor VO, Adebayo OG, Fokoua AR, Moke GE, Ejukolemu EJ, Akpojevughe IO, Abdulkadir AM, Okwuchi E (2024)
Alcohol-exacerbates post-traumatic stress psychiatric behavior and its neuropathological sequalae in experimental mice: preventive effects of morin
Alcohol
:
Ben-Azu B, Toloyai PY, Adebesin A, Ojiokor VO, Adebayo OG, Fokoua AR, Moke GE, Ejukolemu EJ, Akpojevughe IO, Abdulkadir AM, Okwuchi E (2024)
Alcohol
: