About This Project
Addictions to cocaine and other stimulant 'designer' drugs remain unaided by pharmacotherapies. Several decades of work support the use of agents that augment neurochemistry (e.g., dopamine and glutamate transmission) to normalize reward- and mood-governing pathways that become dysregulated following chronic stimulant use. An unexplored but promising route is to test clinically-available antibiotics in models of mood and addiction to holistically evaluate their therapeutic potential.
Ask the ScientistsJoin The Discussion
What is the context of this research?
Research science is beginning to appreciate that bacteria in the gut can augment neurochemistry. Antibiotics certainly alter gut microbiota, but they seem to also exert favorable effects within the brain. Our Center finds that clinically-available antibiotics ceftriaxone and clavulanic acid change levels of protein neuromodulators in brain regions that process rewards and regulate mood.
To determine if antibiotics are capable of favorably regulating addiction-related mood changes, we can record ultrasonic vocalizations (USVs) from rats as they self-administer drugs of abuse. USVs offer the benefit of a sensitive, non-invasive measure of positive and negative mood states in rats.
The proposed Experiment aims to converge these lines of work.
What is the significance of this project?
Our communities deserve more effective treatments for aiding substance use disorders. The most effective smoking cessation aide, for example, helps 1-in-4 people successfully quit after a year of treatment (see summary table).
Clandestine laboratories are rapidly manufacturing synthetic stimulant drugs that cause psychosis, hysteria and delirium. To maintain pace with manufacture of these illicit agents, we urgently need to evaluate potential therapies that are known to be tolerated by humans. These clinically-available compounds hold the greatest promise for making a real and immediate difference.
This Experiment comes at an exciting time to help enhance interpretation of an ongoing Phase I clinical trial sponsored by local institutions (NCT02563769).
What are the goals of the project?
The aim of our Experiment is to assess the degree to which ceftriaxone and clavulanic acid normalize dysregulated mood associated with drug addiction. Rats rapidly elicit 50-kHz USVs ("positive" calls; video) upon exposure to a drug-paired context as well as following receipt of psychostimulant drugs. Conversely, "negative" 22-kHz USVs occur during drug withdrawal.
Procedures for cocaine and MDPV self-administration will follow our prior work. Groups of rats will receive 7-day treatments with ceftriaxone, clavulanic acid or saline (control group). USVs will be measured during self-administration, extinction, and reinstatement tests to fully disentangle relationships between antibiotics, affect and addiction.
The proposed budget provides our team animal subjects, pharmacological compounds, and equipment needed for surgical procedures.
Our experiment will perform routine intravenous jugular vein catheterization surgery to permit stimulant self-administration in rats. Beta-lactam antibiotic compounds (clavulanic acid, ceftriaxone) are available for purchase through Sigma-Aldrich and will be dissolved in saline and injected into rats at multiple time-points.
The following pieces of equipment, graciously provided by the Behavioral Core Facility of the Center for Substance Abuse Research (National Institutes of Health [National Institute on Drug Abuse] P30 DA013429), will additionally be used: 16 rat self-administration chambers, 16 ultrasonic condenser microphones.
Meet the Team
Primary team members include Steve, Cal and Lili within the Center for Substance Abuse Research at Temple University in Philadelphia, PA. We work with one another and exchange ideas on a regular basis as well as with faculty advisers on our floor. We have high-end equipment and enjoy a rich, collaborative work environment. Collectively, we are prepared to see this project through to completion if funded.
SS, CH, LM and RM :-)
Greetings, and sincere thanks for reading our proposal! This is our team's crowdfunding maiden voyage, and we could not be more excited to share our Experiment with you in hopes to see it come through to fruition :-)
I am currently a PhD Candidate within the Center for Substance Abuse Research at Temple University in Philadelphia, PA. I have maintained passionate interest in pre-clinical neuroscience research in substance use disorders for the past 6 years. I am particularly interested in transmitter systems governing mood and motivated behavior. More on my professional attributes can be found via Scopus, ResearchGate, and LinkedIn.
Following graduate school, I aim to pursue a post-doctoral fellowship at an academic or government research institution. I am a member of several professional societies (e.g., Society for Neuroscience, Mid-Atlantic Pharmacology Society, International Behavioral Neuroscience Society) and have held reviewer positions for the Journal of Neuroscience, Psychopharmacology, Drug and Alcohol Dependence and Behavioural Brain Research.
My career goal is to become an independent investigator at an academic or government research institution that utilizes behavioral, neuroanatomical and electrophysiological methods to better understand how chronic drug administration alters activity and architecture of mood-associated neuronal transmission systems.
Dr. Callum Hicks
G'day folks! On behalf of our team, I’d like to welcome you to our Experiment! We are very excited about this project, and we hope you will also find our research interesting and worthwhile.
Like my teammates, I am based at the Center for Substance Abuse Research at Temple University where I work as a Postdoctoral Fellow. After completing my PhD in Sydney, Australia, I moved to the US to further pursue my love for research. My early career has focused on understanding the changes that occur in the brain after drug use, and how we can use this knowledge to develop new and more effective treatments for drug addiction. Alongside my research, I have also devoted my time to teaching and mentoring undergraduate students about the wonderful world of neuroscience. If you would like to read more about my research, please visit my Google Scholar and LinkedIn accounts.
My plan is to start a research laboratory that adopts a multidisciplinary approach to studying drug addiction with my wife, who is also a scientist. I would also like to set up a scholarship that provides training in research and leadership skills to individuals from underprivileged backgrounds.
Hi there! I echo the sentiments of my team when I say: welcome to our Experiment! We're glad to have you here with us and we hope that you find our research as exciting and promising as we do!
Unlike my more esteemed colleagues, I still have a long way to go in academia. I recently graduated from Temple University with a bachelor of science in neuroscience and am currently a post-baccalaureate research assistant here at the Center for Substance Abuse Research at Temple University. I've had the privilege of assisting Muschamp lab with many of their previous projects and am very excited to embark on this new collaborative research venture. For now, the name of the game is to expand the breadth of my neuroscience knowledge through research. I'm excited to see what the future has in store for me!
Hello, and welcome to our Experiment! As a research assistant, I am so humbled to be working with such experienced and accomplished researchers and I cannot wait to get started!
I am currently an undergraduate at Temple University studying neuroscience with a minor in psychology. I hope to continue on my academic path to graduate school after graduation next year and continue to expand my knowledge and experience in the field of research.
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