Endocannabinoid Receptor Deficiency Affects Maternal Care and Alters the Dam's Hippocampal Oxytocin Receptor and Brain‐Derived Neurotrophic Factor Expression

Abstract

Maternal care is the newborn's first experience of social interaction, and this influences infant survival, development and social competences throughout life. We recently found that postpartum blocking of the endocannabinoid receptor-1 (CB1R) altered maternal behaviour. In the present study, maternal care was assessed by the time taken to retrieve pups, pups' ultrasonic vocalisations (USVs) and pup body weight, comparing CB1R deleted (CB1R KO) versus wild-type (WT) mice. After culling on postpartum day 8, hippocampal expression of oxytocin receptor (OXTR), brain-derived neurotrophic factor (BDNF) and stress-mediating factors were evaluated in CB1R KO and WT dams. Comparisons were also performed with nulliparous (NP) CB1R KO and WT mice. Compared to WT, CB1R KO dams were slower to retrieve their pups. Although the body weight of the KO pups did not differ from the weight of WT pups, they emitted fewer USVs. This impairment of the dam-pup relationship correlated with a significant reduction of OXTR mRNA and protein levels among CB1R KO dams compared to WT dams. Furthermore, WT dams exhibited elevated OXTR mRNA expression, as well as increased levels of mineralocorticoid and glucocorticoid receptors, compared to WT NP mice. By contrast, CB1R KO dams showed no such elevation of OXTR expression, alongside lower BDNF and mineralocorticoid receptors, as well as elevated corticotrophin-releasing hormone mRNA levels, when compared to CB1R KO NP. Thus, it appears that the disruption of endocannabinoid signalling by CB1R deletion alters expression of the OXTR, apparently leading to deleterious effects upon maternal behaviour.

Anxiety, Stress, and Fear Response in Mice With Reduced Endocannabinoid Levels

“…This hypothesis is supported by the normal behavior of Dagla 2/2 mice in the social preference test, which indicates that the altered maternal behavior is not due to a generally impaired social interest of the knockout animals. Our hypothesis is also in line with previous studies showing that treatment with rimonabant or deletion of the CB 1 resulted in slower pup retrieval (30,31), whereas nursing was not affected. The authors of this study (31) have also suggested that the increased stress sensitivity of CB1 2/2 mice (24,25) contributed to the deficit in maternal care.…”

“…Our hypothesis is also in line with previous studies showing that treatment with rimonabant or deletion of the CB 1 resulted in slower pup retrieval (30,31), whereas nursing was not affected. The authors of this study (31) have also suggested that the increased stress sensitivity of CB1 2/2 mice (24,25) contributed to the deficit in maternal care. Nevertheless, we Anxiety, Stress and Fear Response in Dagla 2/2 Mice cannot rule out the possibility that a dysfunctional maternal behavior contributed to the anxiety-, fear-, and stress-related behavioral phenotypes.…”

Synapsin IIb as a functional marker of submissive behavior

“…Parturition and maternal care are pivotal social events eliciting hormonal responses, including elevated release of Oxytocin, which is strongly implicated in social interactions 25 . Furthermore, studies demonstrated that dams display elevated defensive behavior postpartum 26 27 .…”

Placental glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase-2 recruitment indicates impact of prenatal adversity upon postnatal development in mice

“…Protein was extracted from placentae and analyzed as previously (Nesher et al, 2015;Schechter et al, 2013), with modifications. Whole frozen placentae were immersed in chilled (4 C) radioimmunoprecipitation assay (RIPA) buffer comprised of 1% Triton X-100, 0.5% sodium deoxycholate, 0.1% sodium dodecyl sulfate and 150 mM sodium chloride in 50 nM tris(hydroxymethyl)aminomethane (pH 8), to which protease inhibitor cocktail (04693159001 Roche, Hod Hasharon, Israel) was added 1:25 to the RIPA buffer, as well as 1 mM sodium orthovanadate, 5 mM ethylenediaminetetraacetic acid (EDTA) and 5 mM sodium fluoride, immediately prior to use.…”