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The present study measured postnatal ultrasonic vocalization (USV) and gene expression to examine potential changes in communication and/or attachment in the offspring of mothers exposed to morphine during adolescence. Offspring of morphine-exposed (Mor-F1), saline-exposed (Sal-F1), or non-handled control (Con-F1) female Sprague-Dawley rats were tested for separation-induced distress calls and maternal potentiation of distress calls during early postnatal development. We also examined relative expression of dopamine D2 receptor and mu opioid receptor (oprm1) mRNA in the nucleus accumbens and hypothalamus in these offspring, as their activity has been implicated in the regulation of postnatal USV in response to maternal separation. The findings indicate that adolescent experiences of future mothers, including their 10 daily saline or morphine injections, can result in significant region-specific differences in gene expression. In addition, these experiences resulted in fewer numbers of separation-induced distress calls produced by offspring. In contrast, augmented maternal potentiation was only observed in Mor-F1 offspring. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:714-723, 2016.

Reproductive experience (i.e. parturition and lactation) leads to persistent alterations in anxietylike behaviour that are influenced by the oestrous cycle. We recently found that repeated administration of the selective oestrogen receptors (ER)α agonist propyl-pyrazole triol (PPT) results in anxiolytic-like behaviours on the elevated plus maze (EPM) in primiparous (but not nulliparous) female rats. The present study examined the effects of the acute administration of PPT on EPM behaviour in primiparous and aged-matched, nulliparous female rats. In addition, corticosterone secretion, corticotrophin-releasing hormone (CRH) gene expression and expression of the immediate early gene product Fos in the paraventricular nucleus (PVN) and amygdala were measured either after EPM testing or in home cage controls. Acute PPT administration significantly modified EPM behaviour as a function of reproductive experience, with nulliparous females tending toward increased anxiety-like behaviours and primiparous females tending toward decreased anxiety-like behaviours. In home cage controls, PPT increased corticosterone secretion in all females; however, both vehicle- and PPT-treated, primiparous females had reduced corticosterone levels compared to their nulliparous counterparts. Significant effects of PPT on CRH mRNA within the PVN were observed after the administration of PPT but only in primiparous females tested on the EPM. PPT also increased Fos expression within the PVN of EPM-exposed females; however, both vehicle- and PPT-treated primiparous females had reduced Fos expression compared to nulliparous females. In the amygdala, PPT increased Fos immunore-activity in the central but not the medial or basolateral amygdala, although these effects were only observed in home cage females. Additionally, both vehicle- and PPT-treated home cage, primiparous females had increased Fos in the central nucleus of the amygdala compared to nullip-arous controls. Overall, these data demonstrate that reproductive experience alters the behavioural response to acute ERα activation. Moreover, the findings suggest that central regulation of the hypothalamic-adrenal-pituitary axis is modified as a consequence of reproductive experience.

Reproductive experience (i.e. pregnancy and lactation) alters a number of physiological and behavioral endpoints, many of which are related to reproductive function and are regulated by oestrogen. For example, reproductive experience significantly attenuates the oestradiol-induced prolactin surge on the afternoon of proestrous and circulating oestradiol levels are reduced at this time. While parity-related effects on oestrogen receptor alpha (ERα) have been observed within the anterior pituitary, there are currently no data regarding possible parity-induced alterations in ERα in the brain. Thus, the purpose of the current study was to examine the effect of parity on the expression of ERα in reproductively relevant brain regions. Moreover, because previous findings have demonstrated that the long-term effects of reproductive experience are often oestrous cycle dependent, ERα was examined at two stages of the oestrous cycle (diestrous and proestrous). Finally, as the expression of ERα is significantly influenced by age, both young and middle-aged females were included in the present study. ERα status was determined using immunohistochemistry in select brain regions involved in the regulation of reproductive behavior in age-matched, cycling primiparous (one pregnancy and lactation) and nulliparous females as well as in age-matched, non-cycling (persistent estrus) 12 month-old primiparous and nulliparous females. Significant shifts in ERα cell numbers were observed in the medial preoptic area and medial amygdala as a consequence of reproductive experience in an oestrous-dependent manner. These findings indicate that significant changes in ERα activity occur in the brain as a function of reproductive experience.

Reproductive experience (i.e. pregnancy and lactation) leads to reduced levels of circulating prolactin in both women and rats. Stimulation of prolactin secretion by dopamine antagonists is also blunted following reproductive experience in both species. Whereas a parity-induced reduction in haloperidol-stimulated prolactin secretion is evident in ovariectomised rats, it is unknown whether a similar attenuation of prolactin secretion is present in reproductively experienced, cycling pro-oestrous rats. The present study examined this possibility. Moreover, to determine possible mechanisms involved in parity-mediated changes in prolactin secretion, both dopamine utilisation within the arcuate nucleus/median eminence and expression of dopamine D 2 receptor mRNA (short and long forms) in the anterior pituitary were measured across the afternoon of pro-oestrous in reproductively experience and inexperienced females. Prolactin secretion was lower on the afternoon of pro-oestrous in primiparous females compared to age-matched, nulliparous controls. In addition, haloperidol-stimulated prolactin secretion was reduced in ovariectomised, reproductively experienced females. Although no differences in dopamine utilisation were observed as a function of reproductive experience, parity did affect the expression of both forms of D 2 receptor mRNA in the anterior pituitary. Compared with nulliparous controls, primiparous females had increased D 2 long mRNA expression at 12.00 h on pro-oestrous as well as increased D 2 short mRNA expression at 14.00 h. Because the ratio of D 2 long /D2 short can significantly effect lactotroph proliferation and prolactin secretion, a shift in relative expression of the two D 2 receptor isoforms within the anterior pituitary of parous females may help account for the reduction in prolactin secretion that occurs following reproductive experience.