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J Appl Physiol 87: 673-682, 1999;
8750-7587/99 $5.00
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Vol. 87, Issue 2, 673-682, August 1999

TRH microdialysis into the RTN of the conscious rat increases breathing, metabolism, and temperature

Carlos Cream, Eugene Nattie, and Aihua Li

Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001

Thyrotropin-releasing hormone (TRH) injected into the retrotrapezoid nucleus (RTN) of anesthetized rats produces a large, prolonged stimulation of ventilatory output (C. L. Cream, A. Li, and E. E. Nattie. J. Appl. Physiol. 83: 792-799, 1997). Here we inject or dialyze TRH into the RTN of conscious rats. In 6 of 17 injections (200 nl, 3.1 ± 1.7 mM), ventilation (VE) increased 31% by 10 min, with recovery by 60 min. With dialysis, each animal of one group (n = 5) received, in random order, 10 mM TRH, 10 mM TRHOH (a metabolite of TRH), and artificial cerebrospinal fluid (aCSF); each animal of a second group (n = 5) received aCSF and 1 mM TRH. TRHOH and aCSF had no sustained effects. TRH (1 mM) increased VE (32%, P < 0.02, by 10 min, with recovery by 60 min), O2 consumption (VO2; 19%, P < 0.03), and body (rectal) temperature (Tre; 0.5°C, P < 0.09). TRH (10 mM) increased VE (78%, P < 0.01, by 10 min, with no recovery at 60 min), VO2 (48%, P < 0.01), and Tre (1.0°C, P < 0.01). TRH also induced arousal. The tissue volume affected in dialysis, estimated by spread of dialyzed fluorescein (332.3 mol wt, mol wt of TRH = 362.4), was 1,580 ± 256 nl for 10 mM (n = 5) and 590 ± 128 nl for 1 mM (n = 5). We conclude that 1) the RTN is involved in the integration of VE, VO2, Tre, and arousal and 2) TRH may establish the responsiveness of RTN neurons.

ventilation-metabolism coupling; fight-or-flight response; arousal; control of breathing


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