Regulation of Mammalian Hibernation. John Thomas Burns Louisiana State University and Agricultural & Mechanical College

Louisiana State University LSU Digital Commons LSU Historical Dissertations and Theses Graduate School 1977 Regulation of Mammalian Hibernation. John Thomas Burns Louisiana State University and Agricultural & Mechanical College Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_disstheses Recommended Citation Burns, John Thomas, "Regulation of Mammalian Hibernation." (1977). LSU Historical Dissertations and Theses. 3097. https://digitalcommons.lsu.edu/gradschool_disstheses/3097 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Historical Dissertations and Theses by an authorized administrator of LSU Digital Commons. For more information, please contact [email protected]. INFORMATION TO USERS Thii material was produced from a microfilm copy of the original document. 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Michigan 48106 USA St John's Road. Tyler s Green High Wycombe. Bucks. England HP10 8HR BURNS, John Thomas, 1943- REGULATION OF MAMMALIAN HIBERNATION, Louisiana State University and Agricultural and Mechanical College, Ph.D., 1977 Zoology Xerox University MicrofilmsAnn , Arbor, Michigan 46106 Regulation of Mammalian Hibernation A Dissertation Submitted to the Graduate Faculty of the Louisiana state University and Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor of Philosophy in The Department of Zoology and Physiology by John Thomas Burns B.A., Wabash College, 1965 M.S., Louisiana State University, 1968 August 1977 EXAMINATION AND THESIS REPORT Candidate: John Thomas Burns Major Field: Vertebrate Zoology T itle of T hesis: Regulation of Mammalian Hibernation Approved: Jlbf U. M ajor Professor and Chairman ) if h )/, r DeanI of the Graduate School EXAMINING COMMITTEE: o Date of Examination: J u n e 2 8 , 1977 ACKNOWLEDGEMENTS Dr. Albert H. Meier encouraged and helped me through out my graduate education. His concise logic and his ability to design meaningful experiments continue to be an inspiration to me. Most of the following studies were based on his ideas. My graduate committee worked diligently to provide just criticism of this dissertation. Several persons helped catch ground squirrels, including Paul Shepard, Pat and Debbie Burns, and my wife Anne. Anne has been a loving wife in addition to working to supply most of our income. My parents and family also have been a source of encour agement and support. TABLE OF CONTENTS Page ACKNOWLEDGEMENTS ....................................... ii LIST OF FIGURES ......................................... iv ABSTRACT ................................................ vi INTRODUCTION ............................................ I MATERIALS AND METHODS ................................ 13 RESULTS ................................................... 24 DISCUSSION .............................................. 53 LITERATURE C I T E D ....................................... 65 VITA ..................................................... 75 iii LIST OF FIGURES Figure Page 1* Daily rhythm in insulin's lethal effects in golden hamsters (Mesocricetus auratus) ....................................... 26 2. Hibernation in alloxan-treated and saline-treated thirteen-lined ground squirrels (Citellus tridecemlineatus) . 28 3. Summer hypothermia in thiouracil- treated and untreated thirteen-lined ground squirrels (Citellus tridecem lineatus ) 31 4. Concentrations of plasma corticosterone at 6 times of day in thirteen-lined ground squirrels (Citellus tridecem lineatus ) maintained on a 14-hour daily photoperiod during February ................. 3 3 5. Concentrations of plasma corticosterone at 6 times of day in thirteen-lined ground squirrels (Citellus tridecem lineatus ) maintained on a 12-hour daily photoperiod during Ma y ....................... 35 6. Plasma corticosterone concentrations in male and female thirteen-lined ground squirrels (Citellus tridecemlineatus) sampled throughout the day during February and M a y .............................. 37 7. Hibernation in thirteen-lined ground squirrels (Citellus tridecemlineatus) during 27 days following injections of prolactin at either 12 or 20 hours after corticosterone injections ........... 39 8. PCPA effects on hibernation in thirteen- lined ground squirrels (Citellus tri decemlineatus) ................................ 42 iv Figure Page 9. Arousal from hibernation in thirteen- lined ground squirrels (Citellus tridecemlineatus) 2 days after handling, saline inj ections, or PCPA injections .... 44 10. PCPA effects on the body weight of male golden hamsters (Mesocricetus auratus) ....................................... 47 11. PCPA effects on the body weights of male and female thirteen-lined ground squirrels (Citellus tridecemlineatus) .... 49 12. PCPA effects on the weight of the paired ovaries, the paired oviducts, and the abdominal fat pads of golden hamsters (Mesocricetus auratus) .............. 51 13. Serotonergic and noradrenergic pathways involved in the regulation of hypothermia and hibernation .............. 63 v ABSTRACT Neural and endocrine mechanisms were investigatea with regard to the regulation of hibernation in thirteen-lined ground squirrels (Citellus tridecemlineatus) and golden hamsters (Mesocricetus auratus). Hibernation in thirteen- lined ground squirrels was inhibited with injections of alloxan (prevents insulin production), p-chlorophenylalanine (PCPA) (blocks serotonin synthesis), and two different temporal relationships of corticosterone and prolactin. Prolactin injections given 20 hours after daily injections of corticosterone for 11 days during the hibernation season prevented hibernation. Prolactin given 12 hours after cor ticosterone markedly reduced the occurrence of hibernation. This effect indicates that a temporal synergism of corticos terone and prolactin may be part of a circannual mechanism that regulates seasonal physiological and behavioral changes in the thirteen-lined ground squirrel. Plasma corticosterone concentrations were greater in May females than in February female ground squirrels and were more constant throughout the day. Alloxan decreases the production of insulin that promotes brain serotonin levels by facilitating the trans port of tryptophan (a precursor of serotonin) into the brain. All results can be interpreted in terms of serotonergic neural mechanisms. A dampened corticosterone rhythm is characteristic of low thyroid activity, which may be expected when brain serotonin levels are high. High thyroid activity may contribute to an inability of thirteen-lined ground squirrels to hibernate during summer; thiouracil treatment allowed the occurrence of hypothermia during summer. PCPA caused weight loss, abdominal fat pad reduction, and weight gains in ovaries and oviducts, changes that contrast with those that occur before and during hibernation. The role of neurotransmitters in the neural control of hibernation was tested in golden hamsters. Profound hypo thermia (6°C esophageal temperature) in cold exposed golden hamsters was induced in animals within hours following the injections of ct-methyl-p-tyrosine (blocking agent for the synthesis of noradrenalin), pargyline, and fluoxetine (agents that enhance serotonergic activities). Injections of the drugs singly or in combinations of two were ineffec tive. Return of the hamsters to room temperature within 4 to 10 hours after induction of hypothermia allowed rewarming and survival. These results suggest that an active seroton ergic system and an inactive noradrenergic system are neces sary for the natural hypothermia of hibernation. The drug- induced

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