Purdue University Purdue e-Pubs Open Access Dissertations Theses and Dissertations 4-2016 The effect of voluntary binge caffeine nda ethanol coexposure on neurobehavioral sensitivity to cocaine in male C57BL/6J mice Brandon M. Fritz Purdue University Follow this and additional works at: https://docs.lib.purdue.edu/open_access_dissertations Part of the Neuroscience and Neurobiology Commons, and the Social and Behavioral Sciences Commons Recommended Citation Fritz, Brandon M., "The effect of voluntary binge caffeine nda ethanol coexposure on neurobehavioral sensitivity to cocaine in male C57BL/6J mice" (2016). Open Access Dissertations. 647. https://docs.lib.purdue.edu/open_access_dissertations/647 This document has been made available through Purdue e-Pubs, a service of the Purdue University Libraries. Please contact [email protected] for additional information. Graduate School Form 30 Updated PURDUE UNIVERSITY GRADUATE SCHOOL Thesis/Dissertation Acceptance This is to certify that the thesis/dissertation prepared By Brandon M. Fritz Entitled THE EFFECT OF VOLUNTARY BINGE CAFFEINE AND ETHANOL CO-EXPOSURE ON NEUROBEHAVIORAL SENSITIVITY TO COCAINE IN MALE C57BL/6J MICE For the degree of Doctor of Philosophy Is approved by the final examining committee: Stephen Boehm Chair Cristine Czachowski Kimberly Kinzig Eric Engleman To the best of my knowledge and as understood by the student in the Thesis/Dissertation Agreement, Publication Delay, and Certification Disclaimer (Graduate School Form 32), this thesis/dissertation adheres to the provisions of Purdue University’s “Policy of Integrity in Research” and the use of copyright material. Approved by Major Professor(s): Stephen Boehm Approved by: Nicholas Grahame 4/15/2016 Head of the Departmental Graduate Program Date THE EFFECT OF VOLUNTARY BINGE CAFFEINE AND ETHANOL CO- EXPOSURE ON NEUROBEHAVIORAL SENSITIVITY TO COCAINE IN MALE C57BL/6J MICE A Dissertation Submitted to the Faculty of Purdue University by Brandon M. Fritz In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy May 2016 Purdue University Indianapolis, Indiana ii For my family and friends iii ACKNOWLEDGEMENTS First and foremost, I want to thank my parents, Dr. Vince and Barb Fritz, for emphasizing the importance of education. This has become a value that is very near and dear to my heart. Without your guidance and encouragement, I would not be writing these words today. As I look back on my journey, I cannot express my gratitude deeply enough for everything you invested in my future. I remember that one day in high school when I swore I would never have anything to do with science. Had you not reminded me the importance of keeping an open mind and seizing opportunity, had you not supported me when I switched my major from American Studies to Psychology, I may not be studying what I love. Thank you for everything and I hope to pass on the same value to my children. To my fiancé, soon to be wife, Sarine Janetsian: you are my rock. I cannot imagine going through graduate school without your love and support. You challenge me to be better scientist and a better person. Science brought us together. You understand me and accept me for my strengths and my weaknesses. You are and forever will be an integral part of any success that I am fortunate enough to enjoy. I cannot wait to see what the future has in store for our life together. I would like to thank my brother Ben Fritz for his encouragement and support. You have always been there to listen to and support me, whether the issue involved school or not. It is special for me to be attending your graduation from the University of Wisconsin iv this May as well. It will be difficult having you all the way over in Japan for 18+ months, but I am so proud of you and excited for you to have this amazing opportunity. To my graduate mentor, Dr. Stephen Boehm: your guidance has helped make me the scientist I hoped I could be. Your support for the ideas of your graduate students has helped them flourish in so many ways that it is difficult to describe. I started out as an overwhelmed and unsure student, wondering if I had it in me to make it through this program. Your faith in me to develop independence greatly increased my self-confidence and consequently, my personal interest and productivity. I am deeply grateful for the success that your mentorship has afforded me. I would like to thank all of my committee members for their constructive critiques and intellectual contributions to my Masters and Dissertation projects. Dr.’s Cristine Czachowski, Nicholas Grahame, Eric Engleman, Julia Chester, and Kimberly Kinzig. Thank you for helping me develop as a scientist. I am very grateful for your time and your interest in my graduate education. Thank you to the former Boehm lab members that taught me the lab skills necessary for success in our lab: Dr. David Linsenbardt, Dr. Laverne Melòn, and Dr. Eileen Moore. I also want to thank current lab members for their support, ideas, and friendship: Chelsea Kasten and Mike Smoker. Thank you to all of the past and present Addiction Neuroscience IUPUI graduate students for your camaraderie and support. Finally, I would like to thank the National Institute on Alcohol Abuse and Alcoholism for the support I have received as a doctoral trainee on our institutional T32 training grant (AA07462). I also want to thank the American Psychological Foundation for supporting my dissertation research. v TABLE OF CONTENTS Page LIST OF FIGURES ......................................................................................................... viii ABSTRACT ........................................................................................................................ x INTRODUCTION .............................................................................................................. 1 General Introduction ...................................................................................................... 1 Caffeinated Alcohol Consumption and its consequences .............................................. 2 Caffeine as the Primary Psychoactive Ingredient in Energy Drinks .............................. 3 Motives for Caffeinated Alcohol Consumption ............................................................. 4 Human Laboratory Studies ............................................................................................ 5 Preclinical Animal Research on Caffeine and Ethanol Combinations........................... 6 Preclinical Mouse Model of Binge Caffeine and Alcohol Co-Consumption ................ 9 Sensitization ................................................................................................................. 11 Cross-Sensitization .................................................................................................... 13 Conditioned Place Preference ...................................................................................... 14 Caffeine and Ethanol: Adenosine, Dopamine, and Implications for Altered Cocaine Sensitivity ..................................................................................................................... 16 Associations between Caffeine, Ethanol, and Cocaine Use: Clinical Observations . 16 Associations between Caffeine, Ethanol, and Cocaine Responsivity: Preclinical Observations .............................................................................................................. 17 Adenosine and Adenosine Receptors ........................................................................ 18 Caffeine Pharmacology and its Behavioral Effects: Adenosine ............................. 19 Ethanol Pharmacology and its Behavioral Effects: Adenosine ............................... 22 Dopamine and Dopamine Receptors ......................................................................... 25 Caffeine Pharmacology and its Behavioral Effects: Dopamine .............................. 27 vi Page Ethanol Pharmacology and its Behavioral Effects: Dopamine ............................... 28 Adenosine and Dopamine Receptor Functional Interactions .................................... 30 Cocaine Pharmacology and its Behavioral Effects: Adenosine ................................ 31 Cocaine Pharmacology and its Behavioral Effects: Dopamine ................................. 33 Pilot Study .................................................................................................................... 36 Study Rationale ............................................................................................................ 36 MATERIALS AND METHODS ...................................................................................... 38 Animals ........................................................................................................................ 38 Drugs and Drinking Solutions ...................................................................................... 38 Drinking-in-the-Dark ................................................................................................... 39 Activity Monitoring ..................................................................................................... 40 Experiment 1: Locomotor Sensitization....................................................................... 40 Experiment 2: Conditioned Place Preference .............................................................. 42 Statistical Analysis ......................................................................................................