Rare case of right ventricular dilatation associated with anomalous pulmonary venous drainage, sinus venosus atrial septal defect and persistent left superior vena cava.

A 34-year-old woman was seen in the emergency department for shortness of breath and chest pain. During a pandemic, it is easy to 'think horses and not zebras', and with a patient presenting with the classic coronavirus symptoms it would have been easy to jump to that as her diagnosis. After a careful history and examination, it became clear that there was another underlying diagnosis. Chest X-ray, echocardiogram and CT scan revealed marked right ventricular dilatation and pulmonary hypertension, alongside a persistent left superior vena cava (PLSVC). Further investigation with cardiac MRI and coronary angiography at a tertiary centre demonstrated that she not only have a PLSVC but also a partial anomalous pulmonary venous drainage and sinus venosus atrial septal defect. This case highlights the importance of considering all differentials and approaching investigations in a logical manner.

Deconstructing early life experiences: distinguishing the contributions of prenatal and postnatal factors to adult male sexual behavior in the rat.

In rodents, a pup's experiences in utero and during postnatal development shape its sexual behavior as an adult and how it is perceived by potential mates. We show that the male rat's sexuality is primarily influenced by the postnatal sex ratio of its litter, but not by the litter's prenatal intrauterine sex ratio or the behavior of its mother. Pups from litters with differing prenatal sex ratios were divided into litters with differing postnatal sex ratios. We found that males raised in a female-biased litter exhibited less mounting than males raised in either a male-biased litter or one with an equal sex ratio, and were less attractive to sexually receptive females, eliciting fewer soliciting behaviors, such as hop-darts, and fewer lordosis behaviors. However, the number of intromissions and ejaculations did not differ across groups, which suggests that males from female-biased litters mate as efficiently as males raised in other sex ratios, but do not require as many mounts to do so. The reported differences in sexual behavior did not vary with the quality of maternal behavior or with sexual experience in adulthood.

Effects of gestational stress: 2. Evaluation of male and female adult offspring.

Physical restraint applied during gestation is a commonly employed animal model of human pregnancy stress. The consequences of such a paradigm have been extensively investigated in adult male rats using a variety of physiological and behavioral measures. The behavioral repertoire of female offspring, however, has been largely ignored. The current study examines adult offspring-male and female Long Evans rats (55-90 days of age) and is a follow-up report to the consequences of maternal restraint (gestation days 10 through 19) in mother rats and their juvenile offspring. Physiological measures included weight and estrous cycle regularity. Elevated plus maze and emergence tests were used to measure anxiety, and the T-maze test, cognition. Data were analyzed via hierarchical linear modeling to account for the nesting of offspring within litters. Compared to same-sex controls, males from stressed mothers displayed a progressive attenuated weight gain over experimental weeks while females from stressed mothers maintained a stable, lower weight throughout. Twenty-five percent of females in the stressed group and none in the control group displayed irregular cycles in the first week of testing; on subsequent weeks, this group discrepancy ranged from 1% to 11%. Subtle effects were observed in anxiety measures: an interaction between sex and stress group in the analysis of head dip behavior in the elevated plus maze and decreased emergence latencies in stress groups. Results demonstrate the importance of examining the effects of maternal stress in offspring of both sexes at various developmental stages.

Effects of gestational stress: 1. Evaluation of maternal and juvenile offspring behavior.

In both humans and animals, stress experienced during gestation is associated with physiological changes and disruptions in emotional function and cognitive ability in offspring; however, much less is known about the effects of such stress in mothers. In animal models, physical restraint is commonly employed to induce stress during gestation and results in elevated postpartum maternal anxiety and changes in maternal care. The purpose of the current study was to evaluate the consequences of restraint stress applied on gestation days 10 through 19 in mother rats and their juvenile offspring. Progeny were reared by birth mothers. Preterm anxiety was assessed in the elevated plus maze and maternal behavior in the retrieval test. Cognitive (T-maze) and anxiety measures (elevated plus maze and emergence) were applied to a subset of male and female offspring at 30-31 days of age. Weight and litter characteristics were also recorded. Mother rats exposed to stress during gestation had attenuated weight gain, elevated anxiety-like behavior, and reduced maternal care. Stressed mothers also had fewer pups and an elevated offspring mortality rate. The consequences of gestational stress in offspring were subtle and gender-dependent. Only juvenile females displayed marginal effects of gestational stress in the form of elevated anxiety-like behavior and attenuated weight gain. In the current study, although gestational stress had robust effects in the mother rat, these did not translate to similar changes in offspring behavior. The importance of focusing research on maternal responses to gestational stress is highlighted by these findings.

Effects of early deprivation and maternal separation on pup-directed behavior and HPA axis measures in the juvenile female rat.

Juvenile female rats show maternal-like behavior toward pups. The purpose of the following experiment was to investigate whether the HPA axis, through the use of early separation manipulations that alter HPA functioning in rats, plays a role in the juvenile response to foster pups. Female rats were early deprived or maternally separated for 5 hours daily from PND 2 to 14 and compared to animal facility-reared rats. Deprivation or separation increased CRH-R1 IR in the juvenile PVN, but had no other effects on other HPA measures or on maternal behavior. Pup-exposure during the juvenile period blunted corticosterone levels after acute and repeated pup-exposures when compared to exposure to novelty and conspecifics respectively. Repeated exposures to pups also increased CRH-R1 IR relative to isolation during the juvenile period. Overall, the data suggest that although pup-exposure affects corticosterone levels, the HPA axis does not relate to juvenile maternal behavior in the present experiments.

Maternal isolation alters the expression of neural proteins during development: 'Stroking' stimulation reverses these effects.

Rat pups reared apart from their siblings, mother, and nest environment in the 'pup-in-a-cup' regime show many alterations in behavior reminiscent of the Institutional Inattention/Overactivity Syndrome that characterizes children whose first few months are spent in institutions. In this report, we compare mother-reared (MR) and artificially reared (AR) male rats in concentrations and distributions of brain proteins that are involved in normal brain development. When assessed during the juvenile period and in adulthood, AR animals showed elevations in Neu-N (a neuronal marker) and in S-100 (an astrocyte marker) but reductions in synaptophysin (synapse protein), N-CAM (cell-adhesion molecule), GAP-43 (axon elongation protein), and BDNF (brain derived neurotrophic factor) in comparison to MR controls in many brain sites involved in attention, impulsivity, activity, and social behavior. Daily 'licking-like' stimulation provided to AR animals (AR-MAX) throughout early development that reverses many of the behavioral deficits, also reverses many of the isolation effects on brain proteins. Study 2 showed that elevations in the number of neurons in combination with decreases in functionality are associated with a reduction in neuronal pruning and apoptosis during the very early post-partum period in AR animals and their reversal through daily 'licking-like' stimulation.

Early deprivation, but not maternal separation, attenuates rise in corticosterone levels after exposure to a novel environment in both juvenile and adult female rats.

Separation from the maternal nest alters the hypothalamic-pituitary-adrenal (HPA) axis stress response in adult male rats, but little research has addressed how separation affects female rats. The following experiments investigated how early maternal separation from postnatal day (PND) 2 to 14 affected stress-induced corticosterone and ACTH after exposure to an open field in juvenile and adult female rats. Female rats were separated for 5 h daily from mother and littermates (early deprivation: ED), separated from mother but not littermates (maternal separation: MS), or animal facility reared (AFR). Male siblings were left with the mother rat during separation. Female rats were exposed to an open field arena either during the juvenile period (PND 30) or during adulthood (PND 80-100). Results show that ED juvenile female rats showed a lower corticosterone stress response than MS and AFR female rats when measured at 5 min post-stress, but no difference at 20 or 60 min post-stress. In adulthood, ED female rats showed comparable elevations of corticosterone as MS and AFR rats at 5 min post-stress but lower elevations at 20 min. In terms of behavior, there were no significant effects of early experience. However, in adulthood, ED and MS rats tended to show a decreased proportion of inner grid crossings of the open field compared to AFR rats, suggesting a tendency for increased anxiety in these two separation groups.

The effects of adrenalectomy and corticosterone replacement on induction of maternal behavior in the virgin female rat.

Maternal behavior of the sensitized virgin rat is affected by approach-avoidance systems as well as by hypothalamic-pituitary-adrenal (HPA) axis, which is also activated during stress. The present experiments investigated the effects of adrenalectomy and of varying corticosterone concentrations on the onset and expression of maternal behavior in sensitized virgin rats. In the first experiment, latency to onset of maternal behavior and time spent licking once maternal were positively related to endogenous levels of corticosterone. However, few rats showed licking. In the second experiment, virgin rats were adrenalectomized or given sham surgeries before being sensitized and being given 0, 25, 100, 300, or 500 microg/mL of corticosterone in their drinking water. In the third experiment, virgin rats were adrenalectomized or given sham surgeries and given either control or corticosterone time-release pellets after being sensitized. Maternal behavior was then tested. Adrenalectomy increased licking in the second experiment and time over pups in the third experiment. Corticosterone replacement reduced licking in the second experiment and both licking and time over pups in the third experiment. In conclusion, exogenous corticosterone had an inhibitory effect on the expression of maternal behavior in the sensitized virgin rat, unlike the facilitatory effect previously found in the postpartum rat.

The effects of adrenalectomy and corticosterone replacement on maternal memory in postpartum rats.

Hormones associated with parturition prime rats to behave maternally, although hormonal changes are not necessary for these behaviors to occur. Experience with pups after birth enhances maternal responsiveness after a period of isolation, creating a maternal memory. The purpose of this study was to determine the role of corticosterone in the formation of maternal memory. Adrenalectomy or sham surgeries were performed in late gestation with corticosterone or vehicle pellets being given to adrenalectomized rats. Pups were removed immediately following parturition, and half of the rats received 4 h of pup experience, while the other half received only brief pup experience associated with parturition. Ten days following pup experience, foster pups were given to all rats. Latency to become maternal and maternal behaviors on the first 2 days of re-exposure and the first two maternal days were recorded. Among adrenalectomized rats given corticosterone, 4-h experience with pups decreased maternal latency when compared to brief experience with pups. This maternal experience effect was not found in comparisons between adrenalectomized rats not given corticosterone. In addition, corticosterone decreased latencies regardless of pup experience. Corticosterone also increased maternal behavior upon initial exposure to foster pups. In conclusion, corticosterone enhanced maternal memory and initial maternal behavior in postpartum rats.

The effects of adrenalectomy and corticosterone replacement on maternal behavior in the postpartum rat.

It is well known that the hypothalamic-pituitary-adrenal (HPA) axis is activated during stress. Recent work suggests it is also implicated in the regulation of "normal" behaviors. The present studies investigated the effects of adrenalectomy and of varying glucocorticoid concentrations on adult maternal behavior in primiparous rats. In two studies, rats in late pregnancy were adrenalectomized or given sham surgeries and were tested for maternal behavior. In the first study, primiparous rats were given 0, 25, 100, 300, or 500 microg/ml of corticosterone in their drinking water. In the second study, primiparous rats were given either control or corticosterone time-release pellets. Blood samples were taken to ensure that rats demonstrated levels of corticosterone in blood that were relative to doses received. In studies one and two, primiparous adrenalectomized rats showed slightly, but significantly, lower levels of some maternal behaviors, including licking and time in nest, than primiparous sham rats. Primiparous rats given higher doses of corticosterone replacement showed higher levels of these maternal behaviors than primiparous rats given lower doses of corticosterone. In conclusion, adrenalectomy decreases, but does not abolish, maternal behavior. Corticosterone replacement reverses these effects. Corticosterone is not necessary for the initiation or maintenance of maternal behavior but plays a role in the modulation of ongoing maternal behavior.

Caffeine as a performance-enhancing drug in rats: sex, dose, housing, and task considerations.

Past animal studies of the performance-enhancing properties of stimulant drugs, such as caffeine, may have suffered from a number of procedural and ethical problems. For example. the housing condition of the animals was often not taken into consideration. As well, endurance tests, such as the forced swim task, sometimes involved ethically (and procedurally) questionable interference with natural swimming behaviour. Some of the manipulations, such as attaching a weight to the swimming animal's tail to increase the difficulty of the task and using mortality as a dependent variable, seem grotesque, even unnecessary. In this experiment, the performance-enhancing effects of caffeine in a modified forced swim task and a dominance task were evaluated using male and female rats as subjects (N=60), housed in either enriched or isolated environments. Analysis indicated that rats respond to caffeine as an interactive function of sex, housing, dose, and task characteristics. It was concluded that performance-enhancing properties of stimulant drugs may be the result of a complex interplay of variables, making simple generalizations questionable.

Mothering begets mothering: the transmission of behavior and its neurobiology across generations.

Early experiences exert their effects on adult parental behavior in part by altering the development of neurobiological mechanisms that initiate or support the initiation and sustenance of adult parental behavior. The effects of parental behavior on sensory, perceptual and emotional mechanisms in offspring constitute an experientially based mechanism by which neurobiological factors regulating behavior can be transferred from generation to generation somewhat independently of genetic endowment.