title: Chemical stimulation of the dorsomedial hypothalamus evokes non-shivering thermogenesis in anesthetized rats.
abstract: Disinhibition of neurons in the dorsomedial hypothalamus (DMH) by microinjection of the GABA(A) receptor antagonist bicuculline methiodide (BMI) elicits a range of autonomic and endocrine changes resembling those seen in experimental paradigms for emotional stress. Stress in rats is also known to provoke increases in body temperature resulting in part from sympathetically mediated activation of brown fat. The purpose of the present study was to examine the effect of microinjection of BMI into the DMH on core body temperature and temperature of brown fat in rats. In anesthetized preparations, microinjection of BMI 10 pmol/50 nl into the DMH and adjoining posterior hypothalamus elicited marked and rapid increases in temperature in interscapular brown adipose tissue (IBAT) and lesser delayed elevations in rectal temperature. Similar injections into the paraventricular nucleus or ventromedial hypothalamus had no effect on either parameter. Peak increases in IBAT were significantly correlated with both peak increases in core temperature and maximal increases in heart rate that accompanied these changes, and all of these effects were abolished by systemic treatment with propranolol 1 mg/kg. In conscious rats instrumented for telemetry, microinjection of BMI 10 pmol/100 nl into the DMH evoked marked increases in core temperature as well as heart rate, locomotor activity, and plasma ACTH. The increase in core temperature occurred with a delayed time course similar to that seen in anesthetized preparations. These results indicate that activation of neurons in the DMH provokes increases in body temperature resulting in large part from sympathoadrenally-mediated activation of brown fat.
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Drive, MS-A421 Indianapolis, IN 46202, USA.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Zaretskaia
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Zaretsky
authors.forename: Anantha
authors.initials: A
authors.lastname: Shekhar
authors.forename: Joseph A
authors.initials: JA
authors.lastname: DiMicco
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000313:Adrenal Medulla / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology*; D004302:Dorsomedial Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011943:Receptors, Adrenergic, beta; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D000324:Adrenocorticotropic Hormone; D011433:Propranolol; D001640:Bicuculline