Type-1 thyrotropin-releasing hormone receptor in the nucleus accumbens participates in the anorectic effect of the stimulation of central nucleus of the amygdala.

Thyrotropin-releasing hormone (TRH) is a hypothalamic neuropeptide that directs the thyroid axis function. Beyond this classical role, TRH is also synthesized in extrahypothalamic brain regions, where it is implicated with anorectic, anxiolytic and antiepileptic effects. Its anorectic role is supported by the reduced food intake of fasted rats when refed, after TRH is injected into their nucleus accumbens (NAc). The central nucleus of the amygdala (CeA) contains TRHergic cells, and its electrical stimulation (ES) induces a hypophagic effect on rats and transsynaptic changes in TRH content in the NAc and other brain regions. Since the G-protein-coupled type-1-TRH receptor is expressed in the NAc, we evaluated its participation in ES-amygdala-induced feeding regulation by using the electrical amygdaloid kindling model and by injecting antisense oligonucleotides (ASO) against type-1 TRH receptor (TRH-R1) in the NAc of rats. Male Wistar rats with an implanted electrode in CeA received daily ES (1 s, 60 Hz, 1 ms pulses) for seven days; then, fasted 48-h and on day 10, receiving a last ES, and refed for 2 h. Amygdala TRH mRNA expression was analyzed by in situ hybridization, while accumbal pro-TRH content by Western blot and immunohistochemistry. Amygdalar stimulation increased TRH mRNA in CeA, cortical amygdala and medial amygdalar nucleus; pro-TRH content increased in shell of NAc. Importantly, intra-NAc shell administration of ASO targeting TRH-R1, reversed the reduced food intake induced by CeA stimulation. These findings support the functional role of TRH-R1 in the NAc for the CeA electrical stimulation-induced hypophagia observed in re-fed fasted rats.