Modest cold exposures are likely to activate autonomic thermogenic mechanisms due to activation of cutaneous thermal afferents, whereas central thermosensitive neurons set the background tone on which this afferent input is effective. In addition, more prolonged or severe cold exposures that overwhelm cold defense mechanisms would directly activate thermosensitive neurons within the central nervous system. Here, we examined the involvement of the canonical brown adipose tissue (BAT) sympathoexcitatory efferent pathway in the response to direct local cooling of the preoptic area (POA) in urethane-chloralose-anesthetized rats. With skin temperature and core body temperature maintained between 36 and 39°C, cooling POA temperature by ~1–4°C evoked increases in BAT sympathetic nerve activity (SNA), BAT temperature, expired CO2, and heart rate. POA cooling-evoked responses were inhibited by nanoinjections of ionotropic glutamate receptor antagonists or the GABAA receptor agonist muscimol into the median POA or by nanoinjections of ionotropic glutamate receptor antagonists into the dorsomedial hypothalamic nucleus (bilaterally) or into the raphe pallidus nucleus. These results demonstrate that direct cooling of the POA can increase BAT SNA and thermogenesis via the canonical BAT sympathoexcitatory efferent pathway, even in the face of warm thermal input from the skin and body core.
Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid
