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Amy C. Allen Dissertation Food, Friends and Foes: Estrogens and Social Behaviour in Mice by Amy Elizabeth Clipperton Allen A Thesis presented to The University of Guelph In partial fulfilment of requirements for the degree of Doctor of Philosophy in Psychology + Neuroscience Guelph, Ontario, Canada © Amy E. Clipperton-Allen, December, 2011 ABSTRACT FOOD, FRIENDS AND FOES: ESTROGENS AND SOCIAL BEHAVIOUR IN MICE Amy Elizabeth Clipperton Allen Advisor: University of Guelph, 2011 Professor Elena Choleris This thesis investigates estrogens' modulation of three aspects of social cognition (aggression and agonistic behaviour, social learning, and social recognition). Sex-typical agonistic behaviour (males: overt attacks, females: more subtle dominance behaviours) was increased in gonadectomized mice by estrogen receptor alpha (ERα) agonist 1,3,5-tris(4- hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), while non-overt agonistic behaviour was increased in male and female gonadally intact mice by ERβ agonist 7-Bromo-2-(4- hydroxyphenyl)-1,3-benzoxazol-5-ol (WAY-200070). Estrogens also affected the social transmission of food preferences (STFP). Acute estrogen and ERβ agonists WAY-200070 and 2,3-bis(4-hydroxyphenyl)propionitrile (DPN) prolonged the preference for the demonstrated food when administered pre-acquisition, likely by affecting motivation or the nature of the social interaction, while acute PPT blocked the STFP. All mice receiving any of the three treatments chronically showed a prolonged demonstrated food preference, suggesting a loss of ER specificity. Individual differences in social recognition may relate to increased oxytocin (OT) and vasopressin (AVP) mRNA, and ERα and ERβ gene activation, in the medial preoptic area, and decreased mRNA for ERs, OT receptor (OTR), AVP and AVP receptors 1a and 1b in the lateral amygdala. Additionally, dorsolateral septum ERs, progesterone receptor, and OTR may relate to social interest without affecting social recognition. Our and others' results suggest that estrogens, OT and AVP are all involved in social behaviours and mediate social recognition, social learning, social interactions, and aggression. ERs differently modulate the two types of social learning investigated here: ERα is critical for social recognition, but impairs social learning, while ERβ is less important in social recognition, and prolongs the demonstrated food preference in the STFP. This may be due to differences in receptor brain distributions or in downstream neurochemical systems that mediate these behaviours. The results of this thesis suggest that estrogens, through the various systems they modulate, have a key role to play in social behaviour. Further investigations of how estrogens effect change in these systems at the molecular and cellular level, as well as the critical brain areas and downstream effectors involved in these complex behaviours, are needed, and could contribute to therapeutic interventions in socially-based, sexually dimorphic disorders, like the autism spectrum disorders, and women receiving hormone replacement therapy for negative peri- or post-menopausal symptoms. ACKNOWLEDGMENTS This thesis would not have been possible without the help and support of many individuals. I am extremely grateful to my wonderful advisor, Dr. Elena Choleris, who has been both extremely supportive and helped me to move beyond my limitations and do so much more than I would have thought possible. Thank you, Elena. I can’t imagine a better advisor, and I will miss you greatly! I also appreciate the input and advice of Elena and my advisory and examination committees, which have made this document immeasurably better. Additionally, thanks go out to all the undergraduate research assistants over the years; your work was extremely helpful and I wish you all the best in your future endeavours. I would also like to thank the NACS graduate students, without whom I would not have survived this process! Your friendship, support, collaboration and encouragement were invaluable, and I feel very lucky that you were my colleagues, to say nothing of the friendship that developed. In particular, I can’t imagine this experience without my good friend and ‘lab-sister’, Anna Phan. I feel so lucky to have worked and traveled with you, and I will miss you terribly. All my family, both near and far, also deserve thanks. I am grateful for your support throughout my education and for your pleasure in my success. In particular: Mum, Dad and Ben, thank you for being there for me whenever I needed you, and for taking pride in my accomplishments. It means a lot, and it’s wonderful to know that the distance doesn’t matter. Julia, having you in Guelph has been fantastic, and I will miss being able to visit my favourite seamstress and have a cup of tea! Granny, your little presents and notes of encouragement always came when I needed them most. Marou-jan, I appreciate your sympathetic ear, and the wonderful times we always have together. We may be farther apart, and the chats may be on the phone instead of in the driveway, but we’ll always be there for each other. Finally, thank you to Craig, my wonderful husband. You calm me down and help me through every obstacle, and I couldn’t imagine my life without you. I love you. I could not have come this far without the help, support and encouragement of all the above (and likely many more!). I appreciate everything you’ve done, and I hope you realize how important you’ve been, not only in my education, but also in my life. Thank you, and lots of love to you all. iii TABLE OF CONTENTS Abstract...................................................................................................................................... ii Acknowledgments..................................................................................................................... iii Table of Contents.......................................................................................................................iv List of Abbreviations................................................................................................................ xii List of Tables ...........................................................................................................................xiv Chapter 1: General Introduction ..................................................................................................1 1.1. Social Cognition.............................................................................................................2 1.2. Estrogens........................................................................................................................7 1.2.1. Estrogens: What They Are .....................................................................................7 1.2.2. Estrogens: Effects on Non-social Learning...........................................................11 1.3. Social Interaction and Aggression.................................................................................12 1.3.1. Social Interaction and Aggression: Introduction ...................................................12 1.3.2. Social Interaction and Aggression: Effects of Estrogens.......................................16 1.4. Social Learning of Food Preferences.............................................................................20 1.4.1. Social Learning of Food Preferences: Introduction...............................................20 1.4.2. Social Learning: Effects of Estrogens...................................................................24 1.5. Social Recognition........................................................................................................25 1.5.1. Social Recognition: Introduction..........................................................................25 1.5.2. Social Recognition: Effects of Estrogens..............................................................31 1.6. Aims.............................................................................................................................34 Part I: Chapter 2: Effects of an estrogen receptor agonist on agonistic behaviour in intact and gonadectomized male and female mice...................................................................................37 2.1 Abstract.........................................................................................................................38 2.2 Introduction...................................................................................................................40 iv 2.3 Methods.........................................................................................................................44 2.3.1 Animal Housing....................................................................................................44 2.3.2 Experimental Subjects...........................................................................................44 2.3.3 Apparatus..............................................................................................................45 2.3.4 Drug .....................................................................................................................47 2.3.5 Procedure..............................................................................................................48 2.3.6 Statistical Analysis................................................................................................52 2.4 Results...........................................................................................................................54
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