The Combined Effects of Cocaine and Opiate Drugs on Lipid Metabolism in Mg in Vivo and in Vitro
Department
Department of Biomedical and Translational Sciences
Graduate Level
Master’s
Graduate Program/Concentration
Eastern Virginia Medical School - Biomedical Sciences
Presentation Type
Poster Presentation
Abstract
Cocaine is known to dysregulate lipid metabolism and promote lipid droplet-associated microglia (LDAM), which are characterized by sustained activation, defective phagocytosis, and a role in promoting addiction. Polydrug use, such as the combined administration of cocaine and morphine ("speedball"), is known to produce a more addictive phenotype than either drug alone. However, whether speedball induces higher levels of LDAM and lipid dysregulation in vivo and in vitro remains unclear.
This study aims to investigate the combined effects of cocaine and morphine on lipid metabolism and microglial activation through two specific aims. In Aim 1, C57BL/6 mice were administered cocaine and morphine (15 mg/kg each) for 15 days. Brain tissues were collected for cryosectioning and western blotting (WBs) to assess lipid metabolism pathways and lipid droplet formation. Microglial activation status was evaluated using IBA1 immunostaining. Bodipy staining was performed to assess lipid droplet formation. In Aim 2, BV2 microglial cells were exposed to cocaine and morphine (5 µM each) for 24 hours. Lipid synthesis and degradation pathways were examined through western blotting for markers such as CATB, CATD, LC3B, p21, TFEB, and p62.
Results from both in vivo and in vitro studies demonstrated that cocaine and morphine co-exposure led to significant lipid dysregulation, correlating with increased microglial activation.
These findings provide strong evidence that speedball promotes more profound lipid metabolism disturbances in microglia, contributing to exaggerated neuroinflammation. This research offers valuable insights into the mechanisms of polydrug-induced addiction and highlights lipid metabolism as a potential therapeutic target.
Keywords
Polydrug (Speedball), Lipid Metabolism, Microglial Activation, Lipid Dysregulation, Neuroinflammation, Addiction
The Combined Effects of Cocaine and Opiate Drugs on Lipid Metabolism in Mg in Vivo and in Vitro
Cocaine is known to dysregulate lipid metabolism and promote lipid droplet-associated microglia (LDAM), which are characterized by sustained activation, defective phagocytosis, and a role in promoting addiction. Polydrug use, such as the combined administration of cocaine and morphine ("speedball"), is known to produce a more addictive phenotype than either drug alone. However, whether speedball induces higher levels of LDAM and lipid dysregulation in vivo and in vitro remains unclear.
This study aims to investigate the combined effects of cocaine and morphine on lipid metabolism and microglial activation through two specific aims. In Aim 1, C57BL/6 mice were administered cocaine and morphine (15 mg/kg each) for 15 days. Brain tissues were collected for cryosectioning and western blotting (WBs) to assess lipid metabolism pathways and lipid droplet formation. Microglial activation status was evaluated using IBA1 immunostaining. Bodipy staining was performed to assess lipid droplet formation. In Aim 2, BV2 microglial cells were exposed to cocaine and morphine (5 µM each) for 24 hours. Lipid synthesis and degradation pathways were examined through western blotting for markers such as CATB, CATD, LC3B, p21, TFEB, and p62.
Results from both in vivo and in vitro studies demonstrated that cocaine and morphine co-exposure led to significant lipid dysregulation, correlating with increased microglial activation.
These findings provide strong evidence that speedball promotes more profound lipid metabolism disturbances in microglia, contributing to exaggerated neuroinflammation. This research offers valuable insights into the mechanisms of polydrug-induced addiction and highlights lipid metabolism as a potential therapeutic target.