Rostral ventromedial periaqueductal gray: A source of inhibition of the sympathetic outflow to brown adipose tissue

Central inhibitory pathways play a significant role in determining the level of sympathetic outflow to the cold defense efferents in mammals. We tested the hypothesis that neurons in the rostral ventromedial periaqueductal gray (rvmPAG) are a source of inhibitory regulation of the sympathetic nerve activity (SNA) to brown adipose tissue (BAT). In urethane/chloralose-anesthetized, paralyzed, artificially ventilated rats, microinjection of PGE(2) (200 pmol in 70 nl) into the medial preoptic area (POA) or microinjection of the GABA(A) antagonists, bicuculline or SR95531 (60 pmol in 60 nl), into the dorsomedial hypothalamic area (DMH) increased BAT SNA by +853 +/- 176 and +898 +/- 249% of control, respectively. These evoked increases in BAT SNA were reversed by microinjection of bicuculline (60 pmol in 60 nl) into the rvmPAG at the level of the posterior commissure. Microinjection of muscimol (160 pmol in 80 nl) into the rvmPAG increased BAT SNA by an amount (+191 +/- 92% of control) that was significantly (P < 0.05) smaller than the peak increase observed after bicuculline microinjection into the rostral raphe pallidus (+1340 +/- 547% of control), but not different from that observed after transaction of the midbrain posterior to the rvmPAG (+423 +/- 123% of control). We conclude that the rvmPAG contains neurons that exert an inhibitory influence on the sympathetic outflow to BAT. These BAT sympathoinhibitory neurons are, themselves, under a tonic GABAergic inhibition. Blockade of this tonic inhibition reveals an inhibitory influence of rvmPAG neurons that is capable of reversing BAT SNA activations from POA or from DMH. Augmenting the tonic inhibition of rvmPAG neurons elicits a modest increase in BAT SNA. Neurons in rvmPAG provide some, but not all, of the tonic inhibition regulating the discharge of BAT sympathetic premotor neurons in RPa and ultimately the level of thermogenesis in BAT. (C) 2006 Elsevier B.V. All rights reserved.