The effects of blocking corticotropin-releasing hormone on hypocretin-1-induced impairment of maternal behavior and maternal defense in primiparous mice.

Environmental stressors can have a negative impact on maternal behavior. This likely occurs through excess peptides related to stress and arousal. Two of these potentially stress and arousal- related peptides are corticotropin-releasing hormone (CRH) and hypocretin (HCRT). Both CRH and HCRT induce anxiogenic behaviors in animals, and there is much evidence suggesting the peptides facilitate one another. HCRT and CRH also influence maternal behavior in similar ways. Both facilitate maternal behavior at moderate increases from baseline and impair behavior at higher levels. However, due to the bidirectional effects of these two peptides, it is unknown if these peptides affect maternal behavior by direct or indirect effects. In order to investigate how CRH and HCRT work together, this study examined the effects of blocking CRH receptors on maternal behavior after receiving a dose of HCRT-1 (0.3??g) that has previously been shown to decrease pup-directed behaviors and maternal defense. We hypothesized that blocking CRH receptors would rescue these behaviors. On three consecutive days, primiparous dams received counterbalanced intracerebroventricular (i.c.v.) injections of either a CRH antagonist at a low (2.5??g) or high (5??g) dose or a vehicle injection into the lateral ventricles, and then received HCRT-1 at 0.3??g. There were no treatment differences on pup directed behaviors. However, there were dose-dependent decreases in maternal defense observed at the high dose versus low dose of CRH antagonist, such that high dose decreased frequency of attacks and tail rattling. To explore neural activation in these dams following injection of HCRT-1 (0.3??g) or vehicle, immunohistochemistry was used to identify c-Fos activity in the bed nucleus of the stria terminalis (BNST), lateral septum (LS), and the paraventricular nucleus of the hypothalamus (PVN), all areas important to maternal behavior that contain CRH producing cell bodies. Changes in c-Fos activity were not observed between HCRT-1 and vehicle groups. Based on these results, it is possible that the inhibitory effects of HCRT-1 on maternal defense behavior are likely not driven by CRH receptors, but rather these systems work independently to impair maternal defense.Psycholog