Medullary adrenergic neurons contribute to the cocaine- and amphetamine-regulated transcript-immunoreactive innervation of thyrotropin-releasing hormone synthesizing neurons in the hypothalamic paraventricular nucleus.

Cocaine- and amphetamine-regulated transcript (CART)-IR axons densely innervate the thyrotropin-releasing hormone (TRH) neurons in the hypothalamic paraventricular nucleus (PVN), partly arising from neuronal perikarya in the hypothalamic arcuate nucleus. The source of the remaining CART innervation, however, is unknown. We have recently demonstrated that neurons co-containing adrenaline and CART in the C1-3 areas of the medulla project to the PVN. Since adrenergic neurons densely innervate the hypophysiotropic TRH neurons, we raised the possibility that adrenergic neurons contribute to the CART-IR innervation of hypophysiotropic TRH neurons. Combined in situ hybridization and immunocytochemistry was performed to study the colocalization of CART and phenylethanolamine N-methyltransferase (PNMT), the synthesizing enzyme of adrenaline, in axons innervating the hypophysiotropic TRH neurons. PNMT was observed in 44% of CART-IR axons in juxtaposition to the hypophysiotropic TRH neurons and CART-IR was observed in approximately 50% of all PNMT axons in contact with proTRH perikarya in the PVN. We conclude that adrenergic neurons of the medulla give rise to approximately half of the CART-IR axons innervating hypophysiotropic TRH neurons in the PVN, and propose that CART may play important role in the modulation of adrenergic input to the hypothalamic-pituitary-thyroid axis.