Thermogenesis in brown adipose tissue: increase by 5-HT2A receptor activation and decrease by 5-HT1A receptor activation in conscious rats

Neurosci Lett. 2006 Mar 6;395(2):170-4. doi: 10.1016/j.neulet.2005.10.062. Epub 2005 Nov 15.


Body temperature is decreased by 5-hydroxytryptamine 1A (5-HT1A) agonists and increased by 5-HT2A agonists. The present study determined whether changes in interscapular brown adipose tissue (iBAT) thermogenesis contribute to these effects in conscious unrestrained animals. Male Sprague-Dawley rats were pre-instrumented for measurement of iBAT and core temperature and tail artery blood flow one week before experiments. In the first series of experiments, rats were transferred from warm (25-28 degrees C) to cold (5-10 degrees C) environments. This increased iBAT temperature (+1.3 +/- 0.2 degrees C, P<0.01, n = 7) and reduced tail artery flow. Injection of the 5-HT1A agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin, 0.5 mg/kg, s.c.) reversed the increase in iBAT thermogenesis (-1.5 +/- 0.4 degrees C, P<0.01, n = 6), and decreased core temperature (-1.5 +/- 0.4 degrees C, P<0.01, n = 6). Pre-treatment with WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride), a 5-HT1A antagonist, prevented effects of 8-OH-DPAT. In the second series of experiments, injection of a 5-HT2A agonist, DOI (R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride, 0.1 mg/kg, s.c.) increased both iBAT (+1.9 +/- 0.1 degrees C, P<0.01, n = 7) and core temperatures (+1.4+/-0.2 degrees C, P<0.01, n=7), and decreased tail artery blood flow. Subsequent injection of SR 46349B (trans-4-((3Z)3-[(2-dimethylaminoethyl)oxyimino]-3-(2-fluorophenyl) propen-1-yl)-phenol, hemifumarate, 0.5 mg/kg, s.c.), a 5-HT2A antagonist, reduced all these changes. Results indicate that activation of 5-HT1A receptors reduces sympathetic outflow to BAT and that activation of 5-HT2A receptors increases this outflow. Changes in core temperature mediated by brain/spinal pathways regulated by 5-HT1A and 5-HT2A receptors reflect coordinated changes in BAT-mediated heat production as well as changes in heat dissipation via the thermoregulatory cutaneous vascular beds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / innervation
  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Consciousness*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Receptor, Serotonin, 5-HT2A / drug effects
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Tail / drug effects
  • Tail / physiology
  • Thermogenesis / drug effects
  • Thermogenesis / physiology*


  • Receptor, Serotonin, 5-HT2A
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A