Hypocretin‐1 Dose‐Dependently Modulates Maternal Behaviour in Mice

Abstract

Increases in neuronal activity of hypocretin (HCRT), a peptide involved in arousal, and in HCRT-1 receptor mRNA expression have recently been identified in association with lactation. HCRT is released within brain regions regulating maternal behaviour and it is possible that increased HCRT neurotransmission during lactation supports maternal care. The present study examined for the first time the behavioural effects of HCRT on lactating mice. At intermediate doses, intracerebroventricular (i.c.v.) injections of HCRT-1 (0.06 and 0.1 microg) elevated levels of licking and grooming of pups (but not self-grooming) and number of nursing bouts without affecting other behaviours. At the highest dose, HCRT-1 (0.3 microg, i.c.v) delayed latency to nurse, decreased nursing, increased time off nest, and decreased maternal aggression. Intraperitoneal injections of the HCRT-1 receptor antagonist, SB-334867, exhibited a general trend towards increasing time spent low-arched back nursing (P = 0.053) and decreasing licking and grooming of pups while high-arched back nursing (P = 0.052). This suggests that the endogenous release of HCRT, working independently or dependently with other neuromodulators, may be necessary for full maternal behaviour expression. Possible sites of HCRT action in enhancing and impairing maternal care were identified via examinations of c-Fos immunoreactivity in association with i.c.v. HCRT injections. Together, these finding support the idea of HCRT modulating maternal behaviour, with intermediate levels (0.06 and 0.1 microg) supporting (even augmenting) some behaviours, but with levels that are too high (0.3 microg HCRT, i.c.v.), maternal behaviour and aggression are suppressed.

Orexin/Hypocretin System: Role in Food and Drug Overconsumption

“…Gene expression of OX is increased in pregnant and lactating female rats compared to nonpregnant or nonlactating rats (Kanenishi et al, 2004; Sun, Narita, Murata, Honda, & Higuchi, 2003), and the number of OX-expressing neurons is also increased during lactation (Sun et al, 2003). In accord with this, injection of OX-A into the cerebral ventricles or medial preoptic area specifically increases licking and grooming of pups but not of the self, while peripheral or medial preoptic area injections of an OX1R antagonist reduces these behaviors (D’Anna & Gammie, 2006; Rivas, Torterolo, Ferreira, & Benedetto, 2016). It is possible that the increase in OX during the perinatal period also contributes to other behaviors observed in mothers during this time, including disturbed sleep (Bei, Coo, & Trinder, 2015) and increased caloric intake (Whichelow, 1975), which are ultimately tied to care of the offspring.…”

Hypocretin/Orexin Overexpression Induces An Insomnia-Like Phenotype in Zebrafish

“…Strikingly, Hcrt can increase locomotor activity independent of normal circadian oscillations in locomotor activity, and these oscillations dampen the effects of Hcrt overexpression. Because our experiments were performed on larvae, the results are not confounded by previous experience, feeding, thermoregulation, social interactions, or other complex homeostatic processes or behaviors in which Hcrt has been implicated in mammals (Sakurai et al, 1998;Szekely et al, 2002;Yamanaka et al, 2003;Harris et al, 2005;Borgland et al, 2006;D'Anna and Gammie, 2006). Our experiments therefore clarify the primary function of Hcrt and suggest that the most basal and ancestral role of Hcrt signaling is the promotion of wakefulness.…”

GABA enhancement of maternal defense in mice: Possible neural correlates

“…Previous studies have found that isoflurane can depress c-Fos in the spinal cord (Jinks et al, 2002), but elevate it in the hypothalamus in aged rats (Jansson et al, 2004), so it is not clear how isoflurane may have acted in this study, if at all on c-Fos expression. As indicated above, the use of isoflurane in association with injection here was aimed to reduce stress effects of injection and its previous use in association with injection has not been found not to overtly impair aggression or other maternal behaviors (D'Anna et al, 2005;D'Anna and Gammie, 2006;Gammie et al, 2004). Exactly whether or how CDP and isoflurane may interact at the doses used in this study would need to be examined in subsequent experiments.…”

“…or i.p.) 30 min prior to testing does not impair production of maternal aggression or other maternal behaviors ( D'Anna et al, 2005;D'Anna and Gammie, 2006;Gammie et al, 2004). Immediately after injection, each mouse was placed back in the homeroom for 30 min prior to behavioral testing.…”