α2 Adrenergic receptor-mediated inhibition of thermogenesis.

J Neurosci. 2013 Jan 30;33(5):2017-28. Madden CJ, Tupone D, Cano G, Morrison SF. “α2 adrenergic receptor (α2-AR) agonists have been used as antihypertensive agents, in the management of drug withdrawal, and as sedative analgesics”. In this study, the authors investigated the effects of α2-AR agonists as antipyretic agents. Clonidine (α2-AR agonist) was administered into the rostral raphe pallidus area (neurons in this region regulate sympathetic outflow to brown adipose tissue (BAT), which regulates thermogenesis), which inhibited BAT sympathetic nerve activity and thermogenesis. The authors reversed the effects of clonidine injection by administration of α2-AR antagonist idazoxan into rRPa. The effects of α2-AR agonists were also tested using systemic injections of its agonists, which produced responses similar to central administration. An interesting observation in the present study involves the use of CtB as a retrograde tracer from rRPa and pseudorabies virus as a transynaptic tracer from BAT to demonstrate that VLM was the source of catecholaminergic input to the rRPa and these neurons are synaptically connected to BAT. Furthermore, the authors used optogenetic technique to stimulate the neurons in the VLM and thereby activate 2-ARs in the rRPa, which inhibited BAT SNA. Taken together these findings suggest that α2-AR agonist can be used to treat excessive body temperature during fever. -Madhan