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Updated: Jun 10, 2026
A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
Microglia-associated hippocampal NF-κB/NLRP3/Caspase-1 activation in methamphetamine-induced conditioned place
Xuan Fan1, Yuansen Li1, Yuexin Wang1
1Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650000, China.
Background:
Methamphetamine (METH) addiction is frequently accompanied by emotional disturbances and cognitive impairments. Accumulating evidence suggests that microglia-mediated neuroinflammation contributes to substance use disorders; however, its role in METH addiction-related behavioral abnormalities and underlying mechanisms remains incompletely understood.
Methods:
A mouse model of METH-conditioned place preference (CPP) was established using a classical conditioned place preference paradigm. Behavioral alterations, including anxiety-related and cognitive-associated phenotypes, were evaluated using the open field test, novel object recognition test, and Morris water maze. Microglial activation was pharmacologically inhibited with minocycline. The hippocampal NF-κB/NLRP3/Caspase-1/IL-1β inflammatory signaling pathway was examined by RT-qPCR and Western blotting.
Results:
METH-treated mice developed a robust CPP, confirming successful establishment of the METH-conditioned place preference model. In addition to reward-related behavior, METH exposure induced pronounced anxiety-related behavioral alterations and learning and memory deficits. Minocycline administration significantly reduced METH-induced CPP without producing reward effects when administered alone. Moreover, minocycline was associated with improvements in anxiety-related behavioral alterations and improved cognitive performance in METH-addicted mice. At the molecular level, METH addiction was associated with increased mRNA and protein expression of NF-κB, NLRP3, Caspase-1, and IL-1β in the hippocampus. Minocycline treatment was associated with a significant attenuation of the upregulation of NF-κB, NLRP3, and Caspase-1, while the reduction in IL-1β did not reach statistical significance.
Conclusions:
These findings suggest that METH exposure is associated with emotional and cognitive dysfunctions in addition to reward-related behaviors, potentially involving microglia-associated activation of the NF-κB/NLRP3/Caspase-1 signaling pathway in the hippocampus. Targeting microglial activation and neuroinflammatory pathways may represent a potential strategy for further investigation in modulating METH-related behavioral alterations.
