University of Rhode Island DigitalCommons@URI Open Access Master's Theses 1965 The Effects of Chronic Thyroxine and Pargyline Treatment on Locomotor Activity, Blood Pressure, Urinary Electrolytes, Body Weight and Liver and Brain Monoamine Oxidase Activity in Male Albino Rats Maintained on Fixed Caloric Input Angelo Benedict Mendillo III University of Rhode Island Follow this and additional works at: https://digitalcommons.uri.edu/theses Recommended Citation Mendillo, Angelo Benedict III, "The Effects of Chronic Thyroxine and Pargyline Treatment on Locomotor Activity, Blood Pressure, Urinary Electrolytes, Body Weight and Liver and Brain Monoamine Oxidase Activity in Male Albino Rats Maintained on Fixed Caloric Input" (1965). Open Access Master's Theses. Paper 208. https://digitalcommons.uri.edu/theses/208 This Thesis is brought to you for free and open access by DigitalCommons@URI. It has been accepted for inclusion in Open Access Master's Theses by an authorized administrator of DigitalCommons@URI. For more information, please contact [email protected]. THE EFFECTS OF CHRONIC THYROXINE AND PARGYLINE TREATMENT ~ LOCOMOTOR ACTIVITY, BLOOD PRESSURE, URINARY ELECTROLYI'ES, BODY WEIGHT AND LIVER AND BRAIN MONOAMINE OXIDASE ACTIVITY IN MALE ALBINO RATS MAINTAINED ON FIXED CALORIC INPUT BY ANGELO BENEDICT MENDILLO III A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR TIIE DEGREE OF MASTER OF SCIENCE IN PHARMACOLOGY UNIVERSITY OF RHODE ISLAND 1965 ACKNOWLEDGEMENTS The author wishes to sincerely thank the members of the graduate committee for their advice and encouragement. The author gratefully acknowledges the enthusiastic support of Mr. Anthony M. Guarino in preparing the figures and in carrying out the extensive daily protocols of the experiments. The author wishes to express his gratitude for the continued under­ standing and confidence of his parents, Mr. and Mrs. Angelo B. Mendillo, Jr. This investigation was supported by a Public Health Service predoc­ toral fellowship (5 FL-MH 21,095) from the National Institute of Mental Health. ii ABSTRACT The effects of chronic treatment with thyroxine, pargyline , and com~ bined thyroxine and pargyline were simultaneously determined on locomotor activity, systolic blood pressure, urinary sodium and potassium excretion, body weight gains and terminal monoamine oxidase activity in brain and liver of male albino rats . Chronic locomotor exploratory activity was shown to be best measured by comparing only the first 30-minute counts of groups of rats run on alter­ nate days in the actophotometer. Significant (PS 0.05) depression of exploratory activity occurred during 11 days of daily intraperitoneal in­ jection of thyroxine, pargyline or both these drugs concurrently. Rats receiving thyroxine or both thyroxine and pargyline lost weight beginning on day 2 or 1, respectively, but rats receiving pargyline alone lost no weight. Treatment with thyroxine elicited continuous hypertension and apparently in­ creased heart rate and stroke volume ; these first appeared on day 2 and were present 17 treatment days later. After 4 days of treatment with both drugs there was no hypertension, but heart rate and stroke volume appeared in­ creased. Treatment with pargyline alone appeared to reduce these latter effects, and induced continuous hypotension beginning between days 2 and 7. Urinary excretion of sodium and potassium was continually increased after 7 days of treatment with thyroxine, but not with pargyline or with both drugs . TermLnal monoamine oxidase activity in brain and liver was not affected by thyroxine treatment but was completely suppressed in rats receiv­ ing pargyline or both drugs . MASTER OF SCIENCE THESIS OF ANGELO BENEDICT MENDILLO III Approved : Thesis Committee : Chairman'--::::::=;;::::!::=::==::3:~U....-:::)l;;:~~~~2'~~~~E~~b::ls~ UNIVERSITY OF RHODE ISLAND 1965 TABIE OF CONTENTS Page ACKNOWLEDGEMENTS ii ABSTRACT iii TABLE OF CONTENTS • • 1 LIST OF TABIES • 3 LIST OF FIGURES . 6 I . INTRODUCTION • 7 II. SURVEY OF THE LITERATURE 8 A. THE HEMODYNAMIC EFFECTS OF THYROID HORMONE. • 8 B . THE HEMODYNAMIC EFFECTS OF PARGYLINE HCl •• 10 C . THYROXINE, PARGYLINE AND URINARY SODIUM AND POTASSIUM. 14 D. THYROXINE, PARGYLINE AND BEHAVIOR ••• • •••••• 16 E. THE EFFECTS OF THYROID HORMONES ON MONOAMINE OXIDASE 20 Ill. INVESTIGATION. 25 A. OBJECTIVES 25 B. MATERIALS AND METHODS . 25 1. General Considerations and Daily Protocol. 25 2. Blood Pressure Study . 29 3. Activity Studies . 31 4. Urinary Sodium and Potassium Studies 34 5 . Weight Gain Studies •.. 36 6 . Monoamine Oxidase Assay. 37 IV. RESULTS . • 43 V . DISCUSSION 85 2 Table of Contents (Continued) Page A. BLOOD PRESSURE STUDIES • • • 85 B. URINARY SODIUM AND POTASSIUM STUDIES • 87 C. WEIGHT GAIN STUDIES ••••• 88 D. MONOAMINE OXIDASE STUDIES •• 92 E. ACTIVITY STUDIES: THE METHOD. 97 F. ACTIVITY S'TIJDIES: THE EFFEQTS OF THYROXINE AND PARGYLINE ·. 103 G. CORRELATIONS • • • 105 VI. SUMMARY AND CONCLUSIONS •• 106 VII. REFERENCES • 108 LIST OF TABIES Table Page 1 Principal blood pressure study: the effects of chronic thyroxine and pargyline treatment on systolic blood pressure in male albino rats ..•.••.•..••••....•.• 44 2 Supplementary blood pressure study: the effects of chronic, combined thyroxine and pargyline treatment on systolic blood pressure in male albino rats .•.•....•••..... 46 3 The effects of chronic thyroxine and pargyline treatment on urinary sodium excretion in male albino rats ..... 47 4 The effects of chronic thyroxine and pargyline treatment on urinary potassium excretion in male albino rats ..•.• . 49 5 The effects of chronic thyroxine and pargyline treatment on the weight gains of male albino rats. I. Daily weights • . 51 6 The effects of chronic thyroxine and pargyline treatment on the weight gains of male albino rats. II. Cumulative weight gains from day O.•.................... 53 7 The effects of chronic thyroxine and pargyline treatment on the weight gains of male albino rats. III. Daily weight gains . • 55 8 The effects of chronic thyroxine and pargyline treatment on the weight gains of male albino rats. Cumulative weight gains from day O..•...••• . .•••. • •..... 56 9 Partial purification of monoamine oxidase from brain and liver of male albino rats . • . ••• 58 10 Stability study: monoamine oxidase activity in brain and liver of male albino rats. Mitochondria stored at -4o 0 c. 59 11 Terminal brain monoamine oxidase activity in male albino rats . 60 12 Terminal liver monoamine oxidase activity in male albino rats . 61 13 Summary of Tables 11 ann 12. Terminal monoamine oxidase activity in male albino rats. 62 14 Preliminary study: actophotometric method for measuring gross activity in male albino rats. Typical data generated by two untreated groups of rats. Incremental counts per 30 minutes for 6 hours . • . • • . 63 15 Preliminary study: actophotometric method for measuring gross activity in male albino rats. Typical data generated by two untreated groups of rats. Total cumulative counts per hour for 6 hours . • . 65 3 List of Tables (Continued) Table Page 16 Preliminary study: actophotometric method for measuring gross activity in male albino rats. Incidences of significant differences between two untreated groups of rats, using incremental counts per 30 minutes for 6 hours •....• 68 17 Preliminary study: actophotometric method for measuring gross activity in male albino rats. Incidences of significant differences between two untreated groups of rats, using total cumulative counts per hour for 6 hours ...... 69 18-27 The effects of chronic thyroxine and pargyline treatment on locomotor activity in male albino rats. • . 70-79 18 A. Summary of data generated by two vehicle-treated groups of rats. Incremental counts per 30 minutes for 6 hours. • • 70 19 B. Summary of data generated by a group of vehicle-treated rats and by a group of thyroxine-treated rats. Incremental counts per 30 minutes for 6 hours • . • • . • . • • • • . 71 20 C. Summary of data generated by a group of vehicle-treated rats and by a group of pargyline-treated rats. Incremental counts per 30 minutes for 6 hours • . • . • . • • . • • • 72 21 D. Summary of data generated by a group of vehicle-treated rats and by a group of rats treated with pargyline and thyroxine. Incremental counts per 30 minutes for 6 hours • • . • • . • 73 22 E. Summary of data generated by two vehicle-treated groups of ratr. Total cumulative counts per hour for 6 hours. • 74 23 F. Summary of data generated by two vehicle-treated groups of rats and by a group of thyroxine-treated rats. Total cumulative counts per hour for 6 hours • . • . • • • . • . • • • . • • 75 24 G. Summary of data generated by a group of vehicle- treated rats and by a group of thyroxine-treated rats. Total cumulative counts per hour for 6 hours . • . • . • . • • 76 25 H. Summary of data generated by a group of vehicle-treated rats and by a group of rats treated with pargyline and thyroxine. Total cumulative counts per hour for 6 hours. • . • . • . • 77 5 List of Tables (Continued) Table Page 26 Incidences of significant differences between drug-treated and vehicle-treated groups of rats, using incremental counts per 30 minutes for 6 hours .•.•.•••••.•••.••. 78 27 Incidences of significant differences between drug-treated and vehicle-treated groups of rats, using total cumulative counts per hour for 6 hours . • . • . • . • . 79 LIST OF FIGURES Figure Page 1 Principal blood pressure study: the effects of chronic thyroxine and pargyline treatment on systolic blood pressure in male