Drug and behavioural addictions are characterized by an intense and focused pursuit of a single reward above all others. Pursuit of the addictive reward is often compulsively sought despite adverse consequences and better alternative outcomes. Here, we explored the ability of the central amygdala (CeA) to powerfully bias choice, causing specific rewards to be almost compulsively preferred. Rats were trained on an operant choice task in which they could choose to respond on either of the two levers to receive a sucrose reward, one of which was paired with optogenetic stimulation of the CeA using channelrhodopsin-2 (ChR2). Rats developed an almost exclusive preference for the laser-paired reward over the otherwise equal unpaired reward. We found that this preference for stimulation-paired reward persists even when a much larger sucrose reward is offered as an alternative (contingency management) or when this preferred reward is paired with adverse consequences such as progressively larger electric foot shock, time delays or effort requirements. We also report that when challenged with foot shock, a small proportion of these animals (≈20%) retained an exclusive laser-paired reward preference, whereas others began to seek the alternate reward when the shock reached high levels. Lastly, we confirmed that optogenetic CeA stimulation was not independently rewarding if delivered in the absence of a paired sucrose reward. These results suggest a role for the CeA in focusing motivation and desire to excessive levels, generating addiction-like behaviour that persists in the face of more rewarding alternatives and adverse consequences.

Professor Mike Robinson-First and foremost, thank you for allowing me the opportunity to be at the intersection of biology, neuroscience, psychology, and disease for three years. It is truly one of the most remarkable places to be. Your mentorship has shaped the critical thinker, scientist, and doctor in me. I hope you can rest easy knowing that I will never forget that "liking" and "wanting" are different, and that dopamine ≠ pleasure. And that I've sufficient dopamine-driven motivation to correct those who still refer to our favorite neurotransmitter as the pleasure molecule. To the woman who started as my lab manager and colleague and became my fellow graduate student, housemate, friend-Charlotte Freeland, you have been my rock, the glia holding all my neurons together, and I consider you my sister. To my fellow housemates, BA/MA extraordinaires, and future doctors, Shyle Mehta and Selin Kutlu-we have been through hell and back together. Shyle, not only for your humor, but for being truly one of the most kindhearted humans I know. Selin, for your companionship, your inspirational drive and determination, and our cooking (procrastination) adventures. I am confident that both of you will make wonderful physicians someday. Anna Knes-it has been my pleasure getting to teach you everything about optogenetics. I can't wait to hear about what you accomplish as the next opto expert. Olivia Lofaro-½ of our team-thesis. I am so grateful for the opportunities to have spent what felt like endless hours in the basement of Judd with you. Nothing creates a bond quite like doing (crying over) science. Aarit Ahuja-Thank you for being a fearless and hilarious lab partner, and teaching me how to make light of stressful situations in lab. I am so excited to see what you accomplish as a neuroscientist! Hannah Maniates-Thank you for all of hard work and technical support! Animal Care-Thank you for putting your trust in the lab to carry out careful and compassionate science with our furry friends, and for helping whenever we are in need. iv Kaiya and Chloe Robinson-for bringing joy, smiles, and laughter. Your visits always brightened my days, bringing out the child in me and reminding me that life is a gift. Kaiya, you are fearless and I admire that! Though I haven't had the pleasure knowing you as long, Chloe, you seem to be so quietly full of wisdom. I do hope you both grow up to be some version of the princess superhero you dream of now. I'm still trying to become one myself. April Robinson-thank you for your thoughtfulness and support, your baking, and your yoga companionship. Thank you for supporting Professor Robinson so that he can support the lab members. Professor Helen Treloar-you have served as role model during my time at Wes. I've learned so much from you, not only about neuroscience, but about being strong as a woman in science. Thank for you for growing my passion for neuroscience. Professor Matthew Kurtz-I consider myself lucky to have been taught the fundamentals of neuroscience by you no once, but twice; and to hav...