Date of Award

6-2024

Degree Name

Master of Arts

Department

Psychology

First Advisor

Jonathan Baker, Ph.D.

Second Advisor

Lisa Baker, Ph.D.

Third Advisor

Cindy Pietras, Ph.D.

Fourth Advisor

Alan Poling, Ph.D.

Keywords

CPP, cytokine, gut-microbiome, methamphetamine, probiotics, psychoneuroimmunology

Access Setting

Masters Thesis-Open Access

Abstract

Substance use disorders (SUD) represent a global public health crisis with limited effective treatment options. Recent findings implicate the gut microbiome and gut/brain axis in the pathophysiology of SUDs. Several preclinical studies have established that psychostimulants alter gut microbiome composition, but no published studies have assessed behavioral effects of dietary probiotic supplements on drug-induced behavioral changes. This study utilized rodent conditioned place preference (CPP) as a behavioral index of conditioned drug reward to determine if a dietary probiotic supplement alters the behavioral effects of (+)-methamphetamine (METH). Fifty-four adult female Sprague-Dawley rats were randomly assigned to receive either a standard rodent diet or daily supplements of Bio-Kult®, a probiotic supplement in their daily food rations. After four weeks, CPP commenced while dietary treatments continued. Each diet group was randomly assigned to one of three treatment groups: saline (N=9), 0.5 mg/kg METH (N=9), or 2.0 mg/kg METH (N=9). Following a 15-min habituation session to assess time spent on each chamber side, a biased CPP procedure was implemented. Conditioning trials were conducted once per day, with alternating drug and saline conditions over 10 days, while locomotor activity was monitored. On day 12, animals were allowed to explore both chamber sides for 15 min to determine CPP scores. Fecal samples were collected weekly throughout the study for analysis of gut microbiome composition and brains were harvested 72 hours after the last injection. Behavioral results showed that METH increased locomotor activity in both diet groups. CPP was established by METH in the control diet animals, but the probiotic diet animals did not show strong evidence for CPP. These results demonstrate that a commercially available probiotic supplement attenuates the conditioned rewarding effects of METH in female SD rats. Although profiling the microbial communities obtained from fecal samples collected throughout the study will be essential to interpreting these findings, the behavioral results alone support continued exploration of dietary probiotics as a potential complementary treatment for psychostimulant-induced gut dysbiosis. Other future directions include replication of this study with male rats and evaluation of cytokine levels in selected brain regions related to drug reward.

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