Stimulation of CRH‐Mediated ACTH Secretion by Central Administration of Neurotensin: Evidence for the Participation of the Paraventricular Nucleus

Abstract

Central administration of neurotensin (NT) stimulates hypothalamic-pituitary-adrenal (HPA) activity in freely-moving rats. Increases in adrenocorticotropin hormone (ACTH) and corticosterone (B) were observed 15 min following central NT administration and remained elevated for up to 4 h. Of the two NT fragments tested, NT1-8 and NT8-13, only NT8-13 was found to significantly elevate ACTH and B levels. Moreover, NT8-13 activated the HPA axis with a temporal profile similar to NT1-13, suggesting an interaction with the pharmacologically and molecularly characterized NT receptor. Animals pre-treated intravenously with the corticotropin-releasing hormone (CRH) antagonist, alpha-helical CRH, showed attenuated plasma ACTH and B responses to central NT administration. This indicates that CRH receptor activation is necessary for the stimulatory effects of NT on HPA function. Bilateral lesions of the paraventricular nucleus (PVN) of the hypothalamus significantly reduced NT-induced stimulation of ACTH and B release suggesting that the PVN is essential for NT's stimulatory action. Median eminence content studies indicated that acute central NT administration stimulates CRH, but not arginine vassopressin (AVP), release in animals examined 60 min following NT injection. Taken together, these findings suggest that the stimulatory effects of NT on HPA activity occur via specific NT receptors and that one site of action of NT is likely at the level of the PVN where NT elicits the release of CRH.

Whole-genome resequencing of Xishuangbanna fighting chicken to identify signatures of selection

“…Another gene neurotensin / neuromedin N precursor ( NTS ) encodes a common precursor for neurotensin (NT) and neuromedin N (NN). NT is involved in interactions with dopamine [38] and corticotropin-releasing factor (CRF) signaling [39], two neurotransmitter systems known to modulate aggressive behavior [40, 41]. Furthermore, NT mRNA levels were shown to be significantly reduced in high maternal aggression mice [42].…”

Endogenous CNS Expression of Neurotensin and Neurotensin Receptors Is Altered during the Postpartum Period in Outbred Mice

“…The PVN is of interest because it is involved in maternal behaviors and also regulates HPA activity [52]–[54]. Ntsr1 dependent mechanisms also modulate HPA axis activity in the PVN [34], [35]. The down-regulation of Ntsr1 expression in the postpartum PVN could reflect or contribute to attenuation of the HPA axis, which occurs in postpartum females [55].…”

“…NT signaling is often linked to dopamine signaling in various regions [29], [30], and dopamine itself has been linked to maternal care [31]–[33]. In addition to modulating the activity of the hypothalamic pituitary adrenal (HPA) axis [34], [35], NT release and activation of NT receptors have been shown to affect temperature regulation [36], [37] and pain perception [38]. Further, NT has been linked to some mental health disorders, including schizophrenia and autism [39]–[41].…”

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

“…Among these, corticotropin-releasing factor (CRF), cholecystokinin (CCK), and tachykinins (substance P and neurokinin A and B) have been the most extensively studied, but the involvement of other neuroactive peptides such as neuropeptide Y, arginine vasopressin, nociceptin/orphanin FQ, and neurotensin has also been examined (Aguilera and Rabadan-Diehl, 2000;Griebel, 1999b;Rowe et al, 1995;Smith and Moran, 2001). Specific and highly potent non-peptide receptor ligands have been discovered and developed for most of these peptides Calo et al, 2000a;Dunlop, 1998;Gully et al, 1993;McCarthy et al, 1999;Serradeil-Le Gal et al, 2002).…”