Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

The Role of the Sympathetic Nervous System in the Hypothermic Effect of d-Fenfluramine

Subramanian, Srividya (2002) The Role of the Sympathetic Nervous System in the Hypothermic Effect of d-Fenfluramine. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

PDF (The Role of the Sympathetic Nervous System in the Acute Hypothermic Effect of D-Fenfluramine)
Primary Text

Download (781kB) | Preview
PDF (Title)
Supplemental Material

Download (4kB) | Preview
PDF (Abstract)
Supplemental Material

Download (48kB) | Preview
PDF (Foreword)
Supplemental Material

Download (72kB) | Preview
PDF (Table of Contents)
Supplemental Material

Download (87kB) | Preview
PDF (Chapter I. Overview)
Supplemental Material

Download (494kB) | Preview
PDF (Chapter V. Evaluation of the Effects of d-Fenfluramine on the Cutaneous Vasculature and Total Metabolic Heat Production)
Supplemental Material

Download (315kB) | Preview
PDF (VI. Bibliography)
Supplemental Material

Download (126kB) | Preview


Experiments in this dissertation were conducted to characterize the effects of d-fenfluramine on body temperature and the mechanisms by which d-fenfluramine alter body temperature. The experiments were conducted in conscious male Sprague-Dawley rats. Body temperature was measured in all animals using telemetry. The results of the experiments indicated that d-fenfluramine altered body temperature in animals kept 28, 22, 16 and 4 degrees Centigrade. D-fenfluramine produced hyperthermia in animals kept at 28 degrees Centigrade and varying degrees hypothermia at normal and cooler ambient temperatures. Further experiments were conducted to explore the effects of d-fenfluramine on brown adipose tissue (BAT) thermogenesis, cutaneous vascular tone and whole body oxygen consumption. In animals kept at 22 and 4 degrees Centigrade, we found that d-fenfluramine activated BAT, as indicated by a decrease in BAT norepinephrine content, to the same magnitude. Thus, the hypothermia seen at normal and cooler ambient temperature was not due to lack of BAT activation. Also, activation of BAT by d-fenfluramine was mediated through the sympathetic nervous system and through release of central serotonin, since ganglionic blocker pentolinium and serotonin reuptake inhibitor fluoxetine blocked d-fenfluramine-mediated BAT activation. In animals kept at 16 degrees Centigrade, d-fenfluramine increased tail-skin temperature (Tsk), an index of cutaneous vascular tone, indicating that d-fenfluramine produced cutaneous vasodilation. d-fenfluramine-induced increase in Tsk was mediated through withdrawal of the sympathetic vasoconstrictor tone to the tail, since pentolinium blocks this effect. In animals kept at 28 degrees Centigrade, d-fenfluramine produced a decrease in Tsk, indicating vasoconstriction. The effects of d-fenfluramine on the Tsk were mediated through release of serotonin, since fluoxetine blocked these effects. D-fenfluramine increased whole body oxygen consumption, an index of metabolic activity and the increase was due to BAT activation, since pentolinium prevented the increase. Thus, although d-fenfluramine increased metabolic activity through BAT activation, the increase was insufficient to make up for the heat loss produced by cutaneous vasodilation and thus produces hypothermia. The hyperthermia seen at 28oC is due to activation of BAT and the subsequent inability of the animal to lose the excess heat due to cutaneous vasoconstriction produced by d-fenfluramine at 28 degrees Centigrade.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairVollmer, Regis R.vollm@pitt.eduVOLLM
Committee CoChairEdwards, David J.edj@pitt.eduEDJ
Committee MemberDixit, Balwantbdixit@pitt.eduBDIXIT
Committee MemberAmico, Janetjamico@pitt.eduJAMICO
Committee MemberVyas, Subhash
Date: 3 July 2002
Date Type: Completion
Defense Date: 21 February 2002
Approval Date: 3 July 2002
Submission Date: 9 June 2002
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Body Temperature; Brown Adipose Tissue; Fenfluramine; Fluoxetine; Hyperthermia; Hypothermia; Obesity; Oxygen Consumption; Serotonin. Catecholamines; Sympathetic Nervous System; Thermogenesis; Vasodilation
Other ID:, etd-06092002-180244
Date Deposited: 10 Nov 2011 19:46
Last Modified: 15 Nov 2016 13:44


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item