Presentation Title

Effects of hypocretin receptor 2 antagonism on maternal depression

Faculty Mentor

Kimberly D'Anna-Hernandez

Start Date

23-11-2019 8:00 AM

End Date

23-11-2019 8:45 AM

Location

11

Session

poster 1

Type of Presentation

Poster

Subject Area

behavioral_social_sciences

Abstract

Postpartum depression in lactating mice dams has been shown to diminish maternal behavior and significantly disrupt the mother-infant bond. However, the underlying neuromechanisms of postpartum depression are unclear. Hypocretin (HCRT), a modulatory neuropeptide synthesized in the lateral hypothalamus, may be a candidate. HCRT has 2 receptor subtypes, HCRT receptor 1 (HCRTR1) and HCRTR2. HCRTR2, in particular, regulates processes related to maternal behavior, including wakefulness and arousal. In addition, HCRT neurotransmission is upregulated during lactation and promotes licking and grooming of pups, a rewarding behavior. Thus HCRTR2 may have a role in the expression of postpartum depressive symptoms, which includes decreases in reward and pleasure. The present study seeks to explore whether depressive behaviors are affected by HCRTR2 by antagonizing HCRTR2A and measuring depressive-like behavior in lactating dams. On postnatal day (PND) 4, lactating mouse dams, were given an intraperitoneal (IP) injection of either a high (75mg/kg, ip, n = 10)or low (30mg/kg, ip, n =10) dose of HCRT receptor 2 antagonist (HCRTR2A; EMPA, Tocris) or vehicle solution (n= 10). After 30 min, dams were placed in a 6 minute tail suspension test (TST) to observe time immobile (depressed) vs. mobile (not depressed). There was a significant main effect of HCRTR2A on time immobile in the TST f(2, 27) = 5.89, p= .008. Vehicle treated dams (M= 110.90,SD= 62.70) showed significantly less immobility than the low dose (M= 177.30, SD= 46.52) , t= -3.06, p = .005, or the high dose (M = 173.20, SD= 30.85), t = -2.87, p= .008. The two doses of HCRTR2A did not differ from each other (t = 0.189,p= .851). These results indicate that blocking HCRTR2 increases depressive-like symptoms, indicating that the HCRTR2 subtype may be important in postpartum depression.

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Nov 23rd, 8:00 AM Nov 23rd, 8:45 AM

Effects of hypocretin receptor 2 antagonism on maternal depression

11

Postpartum depression in lactating mice dams has been shown to diminish maternal behavior and significantly disrupt the mother-infant bond. However, the underlying neuromechanisms of postpartum depression are unclear. Hypocretin (HCRT), a modulatory neuropeptide synthesized in the lateral hypothalamus, may be a candidate. HCRT has 2 receptor subtypes, HCRT receptor 1 (HCRTR1) and HCRTR2. HCRTR2, in particular, regulates processes related to maternal behavior, including wakefulness and arousal. In addition, HCRT neurotransmission is upregulated during lactation and promotes licking and grooming of pups, a rewarding behavior. Thus HCRTR2 may have a role in the expression of postpartum depressive symptoms, which includes decreases in reward and pleasure. The present study seeks to explore whether depressive behaviors are affected by HCRTR2 by antagonizing HCRTR2A and measuring depressive-like behavior in lactating dams. On postnatal day (PND) 4, lactating mouse dams, were given an intraperitoneal (IP) injection of either a high (75mg/kg, ip, n = 10)or low (30mg/kg, ip, n =10) dose of HCRT receptor 2 antagonist (HCRTR2A; EMPA, Tocris) or vehicle solution (n= 10). After 30 min, dams were placed in a 6 minute tail suspension test (TST) to observe time immobile (depressed) vs. mobile (not depressed). There was a significant main effect of HCRTR2A on time immobile in the TST f(2, 27) = 5.89, p= .008. Vehicle treated dams (M= 110.90,SD= 62.70) showed significantly less immobility than the low dose (M= 177.30, SD= 46.52) , t= -3.06, p = .005, or the high dose (M = 173.20, SD= 30.85), t = -2.87, p= .008. The two doses of HCRTR2A did not differ from each other (t = 0.189,p= .851). These results indicate that blocking HCRTR2 increases depressive-like symptoms, indicating that the HCRTR2 subtype may be important in postpartum depression.