Kosten, Therese A.2022-08-092022-08-09May 20222022-05https://hdl.handle.net/10657/10737Rationale: Methamphetamine use disorder (MuD) continues to be a global health problem that results in behavioral changes associated with addiction and neurocognitive decline. Despite the profound burden of this disorder, currently, there are no FDA-approved medications for the treatment of MuD. 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 withdrawal alter the intestinal gut microbiota and characterize withdrawal-induced behavioral changes in male and female rodents. We also sought to explore whether the administration of probiotics alters gut microbial composition and blocks the development of anxiety- and depressive-like behavior in METH-exposed male and female rats. Methods: Male and female Sprague-Dawley rats were administered methamphetamine injections (2 mg/kg; s.c.) or saline injection twice daily with either a combination of probiotics or placebo solution (4 groups/n=8 per group) 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 exposure and its withdrawal altered gut microbial composition; and induced anxiety-like behavior in females and anxiety- and depressive-like behavior in males. Two weeks of supplementation with Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 blocked the development of methamphetamine-induced anxiety- and depressive-like behavior in males and restored gut microbial composition more in females. Conclusions: These findings provide direct evidence that methamphetamine and its withdrawal cause gut dysbiosis in both sexes and that the latter is associated with anxiety- and depressive-like behavior in males. The alternative therapies such as probiotics hold potential in treating METH-induced behavioral changes and restoring gut microbial composition in a sex-specific manner. Our observations 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.application/pdfengThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).MethamphetamineGut-MicrobiotaProbioticsSex differencesMethamphetamine use disorder2022-08-09Thesisborn digital