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Liraglutide Alleviated Alpha-Pyrrolidinovalerophenone (Α-Pvp) Induced Cognitive Deficits in Rats by Modifying Brain Mitochondrial Impairment Publisher Pubmed



Noruzi M1 ; Behmadi H2 ; Sabzevari O3 ; Foroumadi A4 ; Ghahremani MH2 ; Pourahmad J5 ; Hassani S6 ; Baeeri M6 ; Gholami M3 ; Ghahremanian A7 ; Seyfi S8 ; Taghizadeh G9 ; Sharifzadeh M2
Authors
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Authors Affiliations
  1. 1. School of Pharmacy, Semnan University of Medical Sciences, Semnan, Iran
  2. 2. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Toxicology & Pharmacology, Faculty of Pharmacy, Toxicology & Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Toxicology and Pharmacology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  6. 6. Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Drug and Poision Information Centre, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Rehabilitation Research Center, Department of Occupational Therapy, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran

Source: European Journal of Pharmacology Published:2024


Abstract

The use of NPS compounds is increasing, and impairment in spatial learning and memory is a growing concern. Alpha-pyrrolidinovalerophenone (α-PVP) consumption, as a commonly used NPS, can impair spatial learning and memory via the brain mitochondrial dysfunction mechanism. Liraglutide isone of the most well-known Glucagon-Like Peptide 1 (GLP-1) agonists that is used as an anti-diabetic and anti-obesity drug. According to current research, Liraglutide likely ameliorates cognitive impairment in neurodegenerative conditions and substance use disorders. Hence, the purpose of this study is examining the effect of Liraglutide on α-PVP-induced spatial learning and memory problems due to brain mitochondrial dysfunction. Wistar rats (8 in each group) received α-PVP (20 mg/kg/d for 10 consecutive days, intraperitoneally (I.P.)). Then, Liraglutide was administered at 47 and 94 μg/kg/d, I.P., for 4 weeks following the α-PVP administration. The Morris Water Maze (MWM) task evaluated spatial learning and memory 24 h after Liraglutide treatment. Bedside, brain mitochondrial activity parameters, including reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), cytochrome c release, mitochondrial outer membrane damage and swelling, and brain ADP/ATP ratio, were studied. Our results showed that Liraglutide ameliorated α-PVP-induced spatial learning and memory impairments through alleviating brain mitochondrial dysfunction (which is indicated by increasing ROS formation, collapsed MMP, mitochondrial outer membrane damage, cytochrome c release, mitochondrial swelling, and increased brain ADP/ATP ratio). This study could be used as a starting point for future studies about the possible role of Liraglutide in ameliorating mitochondrial dysfunction leading to substance use disorder- induced cognitive impairment. © 2024 Elsevier B.V.
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