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The effects of acute and repeated methylenedioxypyrovalerone (MDPV) administration on striatal transcriptome networks
Christopher J Martyniuk1, Marjory Pompilus2, Jordan Schmidt1
1Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32611 USA.
Abstract:
The psychoactive drug methylenedioxypyrovalerone (MDPV) elicits feelings of euphoria and hyperexcitability, but can also result in paranoia, agitation, and depression by unknown mechanisms. We identified molecular networks in the rat striatum that were affected by single or repeated exposure to MDPV. Male Long Evans rats were injected with either saline or MDPV (1 mg/kg) (single or repeated MDPV) over 5 days. To distinguish the effects of repeated MDPV from a single exposure, an additional group received saline over 4 days and then MDPV on the 5th day. Twenty-four hours after the final injection, the left dorsal striatum was processed for transcriptomics. The transcriptome response was subtle after 24 h, and a single gene passed an FDR correction (LOC103691845) following repeated MDPV treatment. Gene set and subnetwork enrichment analyses were conducted to improve data interpretation from a network perspective. Consistent with the mode of action of MDPV, networks related to the nigrostriatal dopaminergic system were altered in the rat striatum. Transcriptional networks related to cognition, short and long-term memory, and synaptic transmission were over-represented in the striatum of rats repeatedly injected with MDPV. This study identifies potential transcriptional networks altered by single or repeated MDPV exposure, which can be interrogated further to elucidate molecular mechanisms underlying cathinone abuse.
Insights
Methylenedioxypyrovalerone (MDPV) alters brain networks involved in memory and cognition. This study reveals molecular changes in the rat striatum following MDPV exposure, offering insights into cathinone abuse mechanisms.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Methylenedioxypyrovalerone (MDPV) is a psychoactive drug known for its stimulant effects.
- The precise molecular mechanisms underlying MDPV's effects, including its potential for paranoia and depression, remain largely unknown.
- Understanding MDPV's impact on brain circuitry is crucial for addressing cathinone abuse.
Purpose of the Study:
- To identify molecular networks in the rat striatum affected by single or repeated exposure to MDPV.
- To investigate the transcriptional changes induced by MDPV in the brain.
- To elucidate the neurobiological underpinnings of MDPV's psychoactive effects.
Main Methods:
- Male Long Evans rats were administered either saline or MDPV (1 mg/kg) through single or repeated injections over 5 days.
- Transcriptomic analysis of the dorsal striatum was performed 24 hours after the final injection.
- Gene set and subnetwork enrichment analyses were employed to interpret network-level changes.
Main Results:
- A single gene (LOC103691845) showed significant changes after repeated MDPV treatment, indicating a subtle transcriptome response.
- Networks associated with the nigrostriatal dopaminergic system were altered, consistent with MDPV's known mechanism of action.
- Transcriptional networks regulating cognition, memory (short and long-term), and synaptic transmission were over-represented in rats repeatedly exposed to MDPV.
Conclusions:
- Repeated MDPV exposure significantly impacts transcriptional networks in the rat striatum, particularly those involved in dopaminergic pathways, cognition, and synaptic plasticity.
- The findings provide a foundation for further research into the molecular mechanisms of MDPV and other cathinones.
- This study highlights potential targets for understanding and treating disorders associated with MDPV abuse.
