Alpha pyrrolidinovalerophenone (α-PVP) administration impairs spatial learning and memory in rats through brain...

Area of Science:

• Neuroscience
• Toxicology
• Pharmacology

Background:

• Novel psychoactive substances (NPS) use is rising, leading to concerns about NPS-induced cognitive decline.
• Alpha-pyrrolidinovalerophenone (α-PVP) is a prevalent NPS, with its effects on cognition and underlying mechanisms largely unstudied.
• Mitochondrial dysfunction is implicated in NPS-induced cognitive impairment.

Purpose of the Study:

• To investigate the impact of α-PVP on spatial learning and memory.
• To explore the role of brain mitochondrial function in α-PVP-induced cognitive deficits.

Main Methods:

• Wistar rats were administered varying doses of α-PVP (5, 10, 20 mg/kg) daily for 10 days.
• Spatial learning and memory were assessed using the Morris Water Maze (MWM) 24 hours after the final dose.
• Brain mitochondrial function was evaluated through assays measuring protein yield, swelling, SDH activity, lipid peroxidation, MMP, ROS, ADP/ATP ratio, cytochrome c release, and MOM damage.

Main Results:

• A high dose of α-PVP (20 mg/kg) significantly impaired spatial learning and memory.
• This high dose also reduced mitochondrial protein yield and disrupted mitochondrial function, evidenced by increased swelling, lipid peroxidation, ROS, cytochrome c release, ADP/ATP ratio, and MOM damage, alongside decreased SDH activity and MMP.
• Lower doses of α-PVP (5 mg/kg) did not affect cognitive performance or mitochondrial function.

Conclusions:

• Repeated administration of α-PVP can lead to impaired spatial learning and memory.
• Brain mitochondrial dysfunction and oxidative stress are likely mechanisms underlying α-PVP-induced cognitive impairments.