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Failure to Replicate an Environmental Effect Of Gibliotheqile nationale 3s Canada t CANADIAN THESES /'+ /'+ FAILURE TO REPLICATE AN-ENVIRONMENTAL EFFECT OF MORPHINE J 1 HYDROCHLORIDE CONSUMPTION: A POSSIBLE PSYCHOPHARMACOGENETIC LIN Bruce Fraser Petrie B.A., Brock University, 1977 M.A., University of Guelph, 1979 THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in the Department of Psychology 0 Bruc,e Fraser Petrie 1985 SIMON FRASER UNIVERSITY - All rights reserved. This work may not be reproduced in whole or in part, by photocopy or other means, without permission of the author. Permission' has been granted L' autorisation a 5tG accordse- - to' the National Library of a la BibliothGque nationale Canada to microfilm this du Canada de microfilmer thesis and to lend or sell cette thsse et de prster ou copies of the film. de vendre des exemplaires du f film. - The author (copyright owner) L' auteur ( titulaire du droit has reserved other d'auteur) se rEserve les publication rights, and autres droits de publication; neither the thesis nor ni 'la th8sel ni de longs extensixe extracts from it extraits de celle-ci ne may be printed or otherwise doivent Gtre imprimgs ou reproduced without his/her autrement reproduits sans son written permission. autorisation Ecrite. P ISBN 0-315-30848-6 Name: Bruce Fraser Petrie q. 4 Degree: Ph. D. Psychology Title of Thesis: Failure to Replicate an Environmental Effect of I Morphine Hydrochloride Consumption: A Possible Psychopharmacogenetic Link . Exami ning Commi ttee : Chaj rman : Dr. Dale Mi11 er-, Ph. D. D rr Senior Supervisor - - \ '-.. Drl'Barry - Beyerstei GPh. D. \ L . - , r --- - Dr. Rafiofidvok$. , man, Ph.D. Dr. thri-itopher baCi mi.D. Dr. Michael E. Corcoran, Ph.D. External Exami ner Professor Department of Psycho1ogy University of Victoria '? PARTIAL COWRIGHT LICENSE I hereby grant to Simon Fraser University the right to lend dissertation (the title of which is shown below) to users of the Simon Fraser University Library, and to make partial or single copies only for such users or in response to a request from the 1 i brary of any other university, or other educational institution, on its own behalf or for one of its users. I further agree that permission for rnultGple copying of this thesis for scholarly purposes may be granted by me or the Dean of Graduate Studies. It is understood,.that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Title of Thesis/Dissertation: Failure to Reol icate an Fnvironmental Effect of Morohine Hvdrochlori de, Consumption: A Possible Ps~cho~harmacoaenetic - Link. Author: . .- - .. (~i~riature) \ Bruce Fraser Petrie (~ame) I ABSTRACT s- - 'i- f The role of differential housing on sucrose-morehink , - 1 .+ consumption in Wistar rats was investigated in two studfes. The -4' results of earlier studies indicating rats housed i6-a quasi-natural colony drank significantly less sucrose-morphine than rats isolated in standard laboratory cages could not be . - 1 replicated. The reason for the nonreplications is the reduced consumption of sucrose-morphine by the isolated animals in the present two studies, a phenomenon noted by other Canadian psychopharmacologists using the same outbred rat strain. The possibility exists that during a colony'converscion the supplier inadvertently introduced strain differences making the present rats more resistant to xenobiotic consumption. Discussion documents the role of genetics in morphine consumption, and suggests future basic psycho~harmacological work be .conducted with inbred animals. 'I -- ACKNOWLEDGEMENTS I wish to express my deep appreciation to Gaye Petrie, Geoffrey, Jennifer and Andrea Petrie, Frank and Agnes Petrie, and Bert aflMarie Thompson for all the encouragement and support they have shown me during this project. -- - I would like to thank Dick Jol, M.L.A.T. and Loekie van der < Wal, R.L.A.T. for their advice and caring of the animals used in this study. I would also like to thank Howard Gabert, P.Eng., Mr. Malcolm Toms, and Wayne Tressel, C.E.T. for their technical expertise and servicing of the equipment used during the data collection phase of this project. I wish to express my gratitude to John Emes, Ph.D., Gordon .Handford, B.A., David Martin, B.Sc., and Gene SF kurhan, M.Sc. in the Basic Health Sciences Department at the British Columbia Institute of Technology for their encouragement, expertise, help and advice in the writing of the discussion section of this paper. ' I am also grateful for the'support of my committee members, Bruce Alexander, Ph.D., Barry eyer stein, Ph.D., and Ray Koopman, Ph.D. I would finally like to thank Anita Turner for the cheerful r and professional manner in which she typed this diss,ertation. %- C TABLE OF CONTENTS Acknowledgements ...........................................iv List of Tables ............................................vii . A. Introduction .............................................. B. Method ..................................................ll Subjects .............'..............................ll Apparatus ............................................ Procedure ..................................:........I3 4 C. Results ...............................................15 "L, Phase 1 ............................................I5 Phase 2 ............................................20 I Phase 3 ..............................:.............20 Phase 4 .............................................30 Phase 5 ............................................35 Phase 6 ............................................35 Phase 7 ...........,.................*..............35 D, Discussion ..............................................49 E. Method ..................................................51 Subjects ...........................................51 Apparatus .........*.................................51 Procedure ...........................................53 F. Results ...-.-.............................................54 - -- G. Discussion ............................................. .58 H. General Discussion and Conclusions ......................59 References ..................................................84 . Personal Communications ..................LC.I...-..-.--L..LC89 -- 7 7 LIST OF TABLES TABLE PAGE Data Summary and Two Way Analysis of Variance on proportion of 10% Sucrose-Water t Wa-ker Consumed in Phase #1 - First 4 Sucrose-Morphine Study ........................ 16 Data Summary and Two Way Analysis of Variance on ~illigramsof 10% Sucrose Ingested per Kilogram of Body Weight in Phase #1 - First Sucrose-Morphine ~tkdy......................... 17 I. Data Summary and Two Way Analysis of Variance on Grams of 10% Sucrose-Water Consumed in Phase' #I - First Sucrose-Morphine Study 18 \ ............... Data Summary and Two Way Analysis of Variance on Grams of Total Fluid Consumpton in Phase #1 - First Sucrose-Morphine Study ....................19 *( Data Summary and Two Way ~nalysisof Variance on Proportion of QS0,-Water to Water Consumed in Phase 82 - First Sucrose-Morphine Study . 2 1 Data Summajy'-I and- Two Way Analysis of Variance on Milligrams of QSO, Ingested per Kilogram of Body Weight in Phase #2 - First Sucrose-Morphine Study 22 - .......................... Data Summary and Two Way Analysis of Variance on Grams of QS0,-Water Consumed in Phase #2 - First Sucrose-Morphine Study ................... 23 Data Summary and TWQ-Way Analysis of Variance on Grams of Total Fluid Consumption in Phase #2 - First Sucrose-Morphine Study ................. 24 Data Summary and Two Way Analysis of, Variance on Proportion of MHC1-Water to Water Consumed in Phase #3 - First Sucrose-Morphine Study . 25 Data Summary and Two Way Analysis of Variance on Milligrams of MHClIngested per Kilogram of Body Weight in Phase #3 - First Sucrose-Morphine Study ......................... 26 .. * Data Summary and Two Way of Variance on Grams of MHC1-Water Consumed in Phase #3 First Sucrose-Morphine Study ..................(j 27 Data Summary and Two Way Analysis of Variance Grams of Total Fluid Consumption in Phase # --First Sucrose-Morphine Study ................. 28 Data Summary and Two Way Analysis of Variance on proportion of MHC1-Water to Water Consumed in Phase #4 - First Sucrose-Morphine Study . 3 1 1 Data Summary and Two Way Analysis of Variance on Milligrams of MHCl Ingested per Kilogram of Body Weight in Phase #4 - First Sucrose-Mo ine Study .................;.. ..... 32 . vK Data Summary and Two Way Analysis of Variance on Grams of MHC1-Water Consumed in Phase #4 - First Sucrose-Morphine Study ................... 33 Data Summary and Two Way Analysis of Variance on Grams of Total Fluid Consumption in phase #4 - First Sucrose-Morphine Study ................. 34 Data Summary and Two Way Analysis of Variance on Proportion of MHC1-Water to Water Consumed in Phase #5 - First Sucrose-Morphine Study . - 36 a LJ Data Summary and Two Way Analysis of Variance on Mi~lligramsof MHCl Iwested per Kilogram 6f Body Weight in Phase #5 - First Sucrose-Morphine Study ......................... 37 4" 19 Data Summary and Two Way Analysis of Variance on Grams of MHC1-Water Consumed in Phase #5 - First Sucrose-Morphine Study 38 - ................... 20 Data summary and Two Way Analysis of Variance on Grams of Total Fluid Consumption in Phase #5 - First Sucrose-Morphine Study ................. 39 2 1 Data Summary and Two Way Analysis of Variance ,on Proportion of MHC1-Water to Water Consumed in Phase #6 - First Sucrose-Morphine Study . 40 P , 22
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