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Updated: Jul 24, 2026
A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
Methamphetamine exposure and its cessation alter gut microbiota and induce depressive-like behavioral effects on rats
Shadab Forouzan1, Kristi L Hoffman2, Therese A Kosten3
1Department of Psychology, Texas Institute for Measurement, Evaluation and Statistics (TIMES), University of Houston, Health and Biomedical Sciences Building 1, 4849 Calhoun Road, Houston, TX, 77204-6022, USA.
Rationale:
Methamphetamine is a highly abused psychostimulant drug and its use remains a major public health concern worldwide with limited effective treatment options. Accumulative evidence reveals the influence of gut microbiota on the brain, behavior, and health as a part of the gut-brain axis but its involvement in modulating this substance use disorder remains poorly understood.
Objective:
We sought to determine whether methamphetamine exposure and cessation or withdrawal alter the intestinal gut microbiota as well as characterize cessation-induced behavioral changes.
Methods:
Male, Sprague-Dawley rats were administered methamphetamine (2 mg/kg; s.c.) or vehicle (n = 8 per group) twice per day for 14 consecutive days. On various days before, during, and after administration, fecal samples were collected and tests of anxiety- and depressive-like behaviors were conducted.
Results:
Methamphetamine administration and cessation did not alter the relative abundance of bacteria but significantly changed the composition of gut bacteria through 16S rRNA sequencing. These changes were normalized after 7 days of methamphetamine cessation. Moreover, acute methamphetamine cessation induced depressive-like behavior, with an increase in immobility in the forced swim test but did not alter anxiety-like behaviors in tests of open field test or elevated plus maze.
Conclusions:
These findings provide direct evidence that methamphetamine and its cessation cause gut dysbiosis and that the latter associates with depressive-like behavior in rodents. Our observation will contribute to a better understanding of the function of gut microbiota in the process of substance use disorders and guide the choice of target therapeutics.
Insights
Methamphetamine use and withdrawal significantly alter gut bacteria composition in rats, with cessation inducing depressive-like behaviors. These findings highlight the gut microbiome
Area of Science:
- Neuroscience
- Microbiology
- Pharmacology
Background:
- Methamphetamine abuse is a global health issue with few effective treatments.
- The gut-brain axis and microbiota influence brain function and behavior, but their role in methamphetamine use disorder is unclear.
Purpose of the Study:
- To investigate how methamphetamine exposure and cessation impact gut microbiota composition.
- To characterize behavioral changes, specifically anxiety and depression, during methamphetamine withdrawal.
Main Methods:
- Male Sprague-Dawley rats received daily methamphetamine or vehicle injections for 14 days.
- Fecal samples were collected for 16S rRNA sequencing to analyze gut microbiota.
- Anxiety- and depressive-like behaviors were assessed using the forced swim, open field, and elevated plus maze tests.
Main Results:
- Methamphetamine administration and cessation altered gut bacteria composition, though not relative abundance.
- Gut microbiota composition returned to normal within 7 days of methamphetamine cessation.
- Methamphetamine cessation induced depressive-like behavior, evidenced by increased immobility, but did not affect anxiety-like behaviors.
Conclusions:
- Methamphetamine use and withdrawal induce gut dysbiosis in rodents.
- Methamphetamine cessation-induced gut dysbiosis is linked to depressive-like behavior.
- Findings suggest gut microbiota as a potential therapeutic target for substance use disorders.
