TRH in the nucleus accumbens acts downstream to α-MSH to decrease food intake in rats

Feeding-regulatory peptides such as thyrotropin-releasing hormone (TRH), alpha-melanocyte-stimulating hormone (alpha-MSH) and their receptors are expressed in brain regions involved in the homeostatic and hedonic control of food intake, such as the hypothalamus and the mesolimbic system, respectively. The nucleus accumbens (NAc) is part of the latter, a brain circuit involved in processing reward stimuli and the appetitive motivation of feeding. When TRH or alpha-MSH are administered in the NAc, both decrease food intake, through activating their respective receptors, TRH-R1 and MC4R. The actions of alpha-MSH as a homeostatic feeding-regulator involves the increase of hypothalamic TRH expression, thus, we aimed to identify whether TRH signaling in the NAc was also participating in alpha-MSH-induced reduction of food intake. alpha-MSH administration in the NAc of 48 h fasted rats reduced their food intake during the 2-h period of refeeding, increased accumbal TRH mRNA expression and decreased that of MC4R. Such downregulated MC4R mRNA levels implied a compensatory decrease of alpha-MSH actions in the NAc after the previous pathway stimulation. The co-administration of alpha-MSH along with an antisense oligonucleotide directed against pro-TRH mRNA in the NAc impaired the alpha-MSH-induced feeding reduction, supporting that the accumbal TRHergic pathway is downstream of alpha-MSH actions to inhibit feeding. Our results suggested that TRH in the NAc mediates some effects of alpha-MSH on inhibition of food intake; this supports the role of TRH not only as a homeostatic regulator but also as modulating the motivational aspects of feeding.