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

Abstract

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 °C) to cold (5–10 °C) environments. This increased iBAT temperature (+1.3 ± 0.2 °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 °C, P < 0.01, n = 6), and decreased core temperature (−1.5 ± 0.4 °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 °C, P < 0.01, n = 7) and core temperatures (+1.4 ± 0.2 °C, P < 0.01, n = 7), and decreased tail artery blood flow. Subsequent injection of SR 46349B ( trans-4-((3 Z)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.