Excitatory amino acid receptors in the dorsomedial hypothalamus mediate prostaglandin-evoked thermogenesis in brown adipose tissue

Neurological Sciences Institute, Oregon Health and Science University, Beaverton, Oregon 97006 Submitted 8 September 2003 ; accepted in final form 13 October 2003 We determined whether the dorsomedial hypothalamus (DMH) plays a role in the thermogenic, metabolic, and cardiovascular effects evoked by centrally administered PGE 2 . Microinjection of PGE 2 (170 pmol/60 nl) into the medial preoptic area of the hypothalamus in urethane-chloralose-anesthetized, artificially ventilated rats increased brown adipose tissue (BAT) sympathetic nerve activity (SNA; +207 ± 18% of control), BAT temperature (1.5 ± 0.2°C), expired CO 2 (0.9 ± 0.1%), heart rate (HR; 106 ± 12 beats/min), and mean arterial pressure (22 ± 4 mmHg). Within 5 min of subsequent bilateral microinjections of the GABA A receptor agonist muscimol (120 pmol·60 nl -1 ·side -1 ) or the ionotropic excitatory amino acid antagonist kynurenate (6 nmol·60 nl -1 ·side -1 ) into the DMH, the PGE 2 -evoked increases were, respectively, attenuated by 91 ± 3% and 108 ± 7% for BAT SNA, by 73 ± 12% and 102 ± 28% for BAT temperature, by 100 ± 4% and 125 ± 21% for expired CO 2 , by 72 ± 11% and 70 ± 16% for HR, and by 84 ± 19% and 113 ± 16% for mean arterial pressure. Microinjections outside the DMH within the dorsal hypothalamic area adjacent to the mamillothalamic tracts or within the ventromedial hypothalamus were less effective for attenuating the PGE 2 -evoked thermogenic, metabolic, and cardiovascular responses. These results demonstrate that activation of excitatory amino acid receptors within the DMH is necessary for the thermogenic, metabolic, and cardiovascular responses evoked by microinjection of PGE 2 into the medial preoptic area. febrile; thermoregulation; sympathetic; glutamate; medial preoptic area Address for reprint requests and other correspondence: C. J. Madden, Neurological Sciences Institute/OHSU, 505 NW 185th Ave., Beaverton, OR 97006 (E-mail: maddench{at}ohsu.edu ).