Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors

Abstract

Naturally occurring variations in maternal licking/grooming influence neural development and are transmitted from mother to female offspring. We found that the induction of maternal behavior in virgin females through constant exposure to pups (pup sensitization) was significantly shorter in the offspring of High compared with Low licking/grooming mothers, suggesting differences in maternal responsivity. In randomly selected females screened for individual differences in maternal responsivity and subsequently mated, there was a significant and negative correlation (r = -0.73) between the latency to exhibit maternal behavior in the pup sensitization paradigm and the frequency of pup licking/grooming during lactation. Females that were more maternally responsive to pups and that showed increased levels of pup licking/grooming also showed significantly higher oxytocin receptor levels in the medial preoptic area, the lateral septum, the central nucleus (n.) of the amygdala, the paraventricular n. of the hypothalamus, and the bed n. of the stria terminalis. Intracerebroventricular administration of an oxytocin receptor antagonist to mothers on postpartum day 3 completely eliminated the differences in pup licking/grooming, suggesting that differences in oxytocin receptor levels are functionally related to maternal behavior. Finally, estrogen treatment of virgin females significantly increased oxytocin receptor binding in the medial preoptic area and lateral septum of female offspring of High, but not Low, licking/grooming mothers. These findings suggest that maternal licking/grooming influences the development of estrogen sensitivity in brain regions that regulate maternal behavior, providing a potential mechanism for the intergenerational transmission of individual differences in maternal behavior.

Figures

Figure 1

(Left) Mean ± SEM latency (days) to exhibit maternal behavior in the virgin female offspring of High (n = 8) and Low (n = 8) licking/grooming mothers. *, P < 0.01. (Right) The percentage of the total number of observations across the first 6 days postpartum in which lactating mothers were observed to be engaged in pup licking/grooming as a function of the latency to exhibit full maternal responsivity in the pup sensitization paradigm in the same animals.

Figure 2

(a) Representative autoradiographic images of [125I]OTA binding in various brain regions in females that were High (full maternal responsivity in <6 days) or Low (full maternal responsivity in >6 days) as determined in the pup sensitization paradigm. MPOA, medial preoptic area; LS, lateral septum; BNST, bed nucleus of the stria terminalis; AMYG, central nucleus of the amygdala; PVN, paraventricular nucleus; VMH, ventromedial nucleus of the hypothalamus. (b) Mean ± SEM levels of [125I]OTA binding (fmol/mg) in day 6 lactating females that were High (full maternal responsivity in <6 days) or Low (full maternal responsivity in >6 days; n = 6 per group).

Figure 3

Mean ± SEM percentage of total observations in which a mother was observed to be licking/grooming a pup (a) or to be in physical contact with pups (b) in High and Low licking/grooming mothers over the first 6 days postpartum. On day 3, all females received an intracerebroventricular infusion of either saline or the oxytocin receptor antagonist [d(CH2)5,Tyr(Me)2,Thr4,Tyr-NH29]-OVT. The frequency of pup licking/grooming in saline-treated High licking/grooming was significantly greater than that of Low licking/grooming mothers on each day of observation. In animals treated with the oxytocin receptor antagonist, differences in licking/grooming were significant only on days 1–2 and 5–6, but not on days 3–4 (n = 8 per group).

Figure 4

(a) Mean ± SEM levels of [125I]OTA binding (fmol/mg) in ovariectomized virgin female offspring of High or Low LG-ABN mothers as a function of estradiol replacement (n = 4–6 per group). *, P < 0.01. (b) Representative autoradiographic images of [125I]OTA binding in various brain regions in ovariectomized virgin female offspring of High or Low LG-ABN mothers as a function of estradiol replacement (see Fig. 2b for list of abbreviations).