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1 Neurological Sciences Institute, Oregon Health & Science University, Beaverton, OR, USA
* To whom correspondence should be addressed. E-mail: morrisos{at}ohsu.edu.
To elucidate the central neural pathways contributing to the thermogenic component of the autonomic response to iv. administration of leptin, experiments were conducted in urethan-chloralose-anesthetized, ventilated rats to address (1) the role of neurons in the rostral ventromedial medulla, including raphe pallidus (RPa), in the leptin-evoked stimulation of brown adipose tissue (BAT) sympathetic nerve activity (SNA) and (2) the potential thermolytic effect of 5-HT1A receptors on RPa neurons that influence BAT thermogenesis. Leptin (1 mg/kg) administration increased BAT SNA by 1219 % of control, BAT temperature by 2.8 °C, expired CO2 by 1.8 %, heart rate by 90 bpm and mean arterial pressure by 12 mmHg. Microinjection of the 5-HT1A receptor agonist, 8-OH-DPAT, into RPa resulted in a prompt and sustained reversal of the leptin-evoked stimulation of BAT SNA, BAT thermogenesis and heart rate, with these variables returning to their pre-leptin control levels. Subsequent microinjection of the selective 5-HT1A receptor antagonist, WAY100635, into RPa reversed the BAT thermolytic effects of 8-OH-DPAT, returning BAT SNA and BAT temperature to the elevated levels following leptin. In conclusion, activation of neurons in RPa, possibly BAT sympathetic premotor neurons, is essential for the increases in BAT SNA, BAT thermogenesis and heart rate stimulated by iv administration of leptin. Neurons in RPa express 5-HT1A receptors whose activation leads to reversal of the BAT thermogenic and the cardiovascular responses to iv leptin, possibly through hyperpolarization of local sympathetic premotor neurons. These results contribute to our understanding of central neural substrates for the augmented energy expenditure stimulated by leptin.
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