Liraglutide alleviated Alpha-pyrrolidinovalerophenone (α-PVP) induced Cognitive deficits in rats by modifying brain mitochondrial impairment.

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 through brain mitochondrial dysfunction mechanisem. Liraglutide, one of the most well-known Glucagon-like peptide 1 (GLP-1) agonist used as an anti-diabetic and anti-obesity drug. According to current research, Liraglutide likely ameliorate cognitive impairment in neurodegenerative conditions and also 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 hours 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 Liraglutide ameliorated α-PVP induced spatial learning and memory impairments through alleviating brain mitochondrial dysfunctions (which is indicated by increasing ROS formation, collapsed MMP, mitochondrial outer membrane damage, cytochrome c release, mitochondrial swelling, and brain ADP/ATP ratio) in rats. This study could be used as a starting point for future studies about the possible role of Liraglutide in mitochondrial dysfunction related to cognitive impairments due to substance use disorder.

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Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: