Opioid receptor blockade during prenatal life modifies postnatal behavioral development

The ontogeny of physical characteristics, spontaneous motor, and sensorimotor behaviors of preweaning rats, as well as ambulation and emotionality at weaning (day 21) were studied in rats exposed to 50 mg/kg naltrexone (NTX) or saline (controls) daily throughout gestation by maternal administration; all animals were cross-fostered to untreated mothers at birth. Morphine challenge tests and nociceptive measures revealed that this dosage of opioid antagonist blocked opioid receptors for 24 h. At birth and weaning, animals in the NTX group weighed 12 and 20%, respectively, more than control offspring. The age at which a specific physical characteristic, spontaneous motor behavior, or reflex initially appeared and the age at which 100% of the animals demonstrated a particular characteristic/behavior often were accelerated in animals prenatally exposed to NTX. The frequency of ambulation was subnormal in the NTX group, and the frequency and/or incidence of rearing, grooming, wet-dog shakes, and defecation were reduced from normal levels in these opioid antagonist-exposed rats. These results imply that interactions of endogenous opioid systems during embryogenesis are determinants of somatic, physical, and behavioral development in postnatal life.     

Abnormal prenatal lung development resulting from maternal zinc deficiency in rats

The effect of maternal zinc deficiency during gestation on fetal lung development was studied. Sprague-Dawley rats were fed from the day of mating (day zero) a zinc deficient diet (0.4 +/- 0.1 ppm zinc) ad libitum, or a zinc supplemented control diet (100 ppm zinc) either ad libitum or with restricted intake. Fetuses were removed by cesarean section on days 17 to 21 of gestation. Fetuses of zinc deficient dams had smaller lungs both in absolute weight and relative to body weight on all days than did either ad libitum-fed or restricted-intake controls. On days 20 and 21 of gestation, concentration of fetal lung lecithin and phosphatidylethanolamine was lower in zinc deficient fetuses than in control groups, indicating a reduced production of pulmonary surfactant. The lecithin to sphingomyelin ratio of amniotic fluid was lower in zinc deficient rats than in controls on days 19, 20, and 21 of gestation. On days 18 through 21 of gestation, fetal lung DNA concentration in zinc deficient fetuses was lower than in controls, but there were no differences in fetal lung zinc concentration. Histological examination of lungs from zinc deficient fetuses at term showed air spaces that were slightly collapsed with smaller lumina of the alveolar ducts than in controls.     

Can prenatal caffeine exposure affect behavioral inhibition?

Given the widespread use of caffeine and its potential nonoptimal effects during pregnancy, it is remarkable and distressing that almost nothing is known about the long-term effects of prenatal caffeine exposure in humans. Research on nonhumans reveals that prenatal caffeine exposure is associated with an enduring tendency toward a profile of fearfulness, hypoactivity, and exaggerated stress in uncertain situations. A similar pattern of behavioral inhibition has been observed in humans and has been attributed to various causes such as inborn temperament or environmental influences. The author's conjecture is that prenatal caffeine exposure could be an additional factor contributing to the tendency toward behavioral inhibition. One mechanism for this effect is that caffeine causes an upregulation of adenosine receptors, thus creating a vulnerability to adenosine-induced inhibition of neuronal firing and neurotransmitter release. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prenatal exposure to N-methylpyrrolidone on postnatal development and behavior in rats

Pregnant rats (Mol:WIST) were exposed to 150 ppm N-methylpyrrolidone for 6 hours per day on gestation days 7-20. The dose level was selected so as not to induce maternal toxicity or decrease viability of offspring. In the preweaning period, the exposed offspring had a lower body weight and their physical development was delayed. Neurobehavioral evaluation of the male pups revealed no effects on basal functions of the central nervous system. The animals appeared normal and motor function (rotarod), activity level (open field), and performance in learning tasks with a low grade of complexity were similar in the two groups. However, in more difficult tasks such as the reversal procedure in Morris water maze and operant delayed spatial alternation (Skinner boxes), performance was impaired in exposed offspring.     

Effects of early prenatal dexamethasone on the cognitive and behavioral development of young children: results of a pilot study

The effect of early prenatal dexamethasone (DEX) exposure on cognitive and behavioral development, behavior problems, and temperament were examined in 26 consecutively identified children aged 6 mo to 5 1/2 years, whose mothers had been DEX-treated during pregnancy because their offspring was at risk for congenital adrenal hyperplasia (CAH), and compared with 14 children from untreated CAH-risk pregnancies. Three children in each group were CAH-affected. Assessments were performed by way of mother-completed standard questionnaires. No significant differences in cognitive abilities or behavior problems were identified. On temperament questionnaires, DEX-exposed children showed more Shyness (p < .004), greater Emotionality (p < .03), less Sociability (p < .04), and a trend for greater Avoiddance (p < .07) than unexposed children. DEX-exposed children also had significantly higher Internalizing (p < .002) and Total Problem scores (p < .05) on the behavior problem measure for 2-3 year olds. The results should be considered preliminary until they have been replicated by the study of a larger sample and direct examination of the children.     

Developmental and behavioral effects of prenatal primidone exposure in the rat

Pregnant Sprague-Dawley rats were administered primidone (PRM) by oral gavage on gestation days 8-17 in doses of 0.40, and 80 mg/kg. Although these doses of PRM did not produce significant differences in litter size, birth weight, mortality, date of attainment of developmental landmarks or measures of preweaning reflex and motor development, there were a number of significant differences that developed as the animals approached and entered adulthood. When tested as adults, the 80 mg/kg male rats showed a deficit in the performance of an eight-arm radial maze task. These same animals showed a significant reduction in open field activity when tested as adults. In addition, both male and female PRM-treated animals showed reduced body weights at different periods corresponding to onset of sexual maturation during development. These findings are consistent with the larger body of literature reporting on the neurobehavioral teratology of phenobarbital, including its ability to produce lesions in the hippocampus and endocrine dysfunction resulting in reproductive deficits. These results suggest that PRM produces its adverse effects as a result of its metabolism to phenobarbital, which in turn affects the limbic system.     

The NMDA and GABA-A receptors in behavioral activity of rats

The effects of bicuculline (0.25 mg/kg ip) and AP-7 (5 nmols icv) on the processes of retrieval, consolidation of conditioned reflexes, object recognition and locomotor activity were tested in rats. AP-7, bicuculline and AP-7 with bicuculline increased (but not significantly) locomotor and exploratory activity in the open field test. Only coadministration of AP-7 with bicuculline facilitated retrieval of passive avoidance in rats, but was without effect on consolidation in this test. AP-7 or bicuculline also did not influence on consolidation, when they were given alone. Object recognition was impaired (but not significantly) in groups of rats treated with bicuculline and bicuculline with AP-7.     

The prenatal development of some of the visual pathways in the cat

Lesions were made in the visual system in a series of cat fetuses of known gestational age, and fiber and terminal degeneration were stained by the Eager method. The times of development of the retinal projection, of the thalamcortical and corticothalamic projections of area 17 of the visual cortex, and of the intrinsic fibers in the visual cortex were examined. Enucleation of one eye resulted in degeneration being detected bilaterally in the lateral geniculate nuclei (LGN), superior colliculi (SC) and optic tracts. The optic nerves reached the optic chiasm by the thirtieth embryonic day (E30) and the optic tract connections with the LGN and SC were made by E37. The projection always appeared stronger in the contralateral LGN and SC, and the amount of degeneration increased in both sides with increasing age. A parasagittal knife cut was made in the dorsomedial crest of the visual cortex. Where the lesion passed through the cellular layers of the cortex, intrinsic fibers were cut when these were present. The deeper part of the incision through the white matter undercut the medial wall of the visual cortex, interrupting thalamocortical and corticothalamic fibers when these were present. The longer horizontal fibers that were intrinsic to the visual cortex began to develop during the last two weeks of gestation but were not fully developed at birth. In the undercut visual cortex distant from the place of entry of the lesion, and before the intrinsic fibers of the cortex had developed, degeneration was found in layers 1 and 4, demonstrating the presence of a thalamocortical pathway. The youngest fetus to show this degeneration was operated at E48. This degeneration was not present three days earlier at E45. Fiber plexuses that have been described earlier in development (Marin-Padilla, '71; Cragg, '75) do not appear to degenerate after undercutting the cortex. The corticothalamic pathway to the lateral posterior nucleus medial to the LGN was developed at E45. The descending pathways to the ipsilateral LGN and SC were developed by E48, but it is not known whether they are present before this. Thus degeneration has been used to detect the development of axonal pathways in the fetus for the first time; the major afferent and efferent pathways are developed at an earlier stage than has previously been described.     

Developmental analysis of behavioral dysfunction in rats with septal lesions.

At 7 days of age, 48 male Long-Evans hooded rats received lesions of the septal nuclei or control operations. Ss then received 30 hrs of training on a DRL 20-sec schedule for 1 hr/day beginning at either 27 or 96 days of age. At 126 days of age, all Ss received 10 additional training sessions. After operant testing, all Ss received 10 additional training sessions. After operant testing, all Ss were tested on spontaneous alternation, spatial reversal, and passive avoidance. Results indicate that on a DRL 20-sec schedule Ss that received lesions of the septum neonatally and were tested at different ages performed in a similar manner. Approximately 50% of the Ss with lesions of the septal nuclei reached efficiency levels comparable with those of normal controls. When tested for retention, these efficient Ss still performed similarly to normal Ss. Ss with septal lesions were facilitated in the acquisition of a spatial habit, were deficient in spatial habit reversal, were less likely to demonstrate spontaneous alternation, and were deficient in passive avoidance. It is concluded that neonatal lesions of the septal nuclei produce permanent behavioral impairments on a diversity of measures and that, although juvenile animals with limbic system damage often manifest behaviors different from adult Ss, the difference is not evident during operant testing (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Motor lateralization, behavioral despair and dopaminergic brain asymmetry after prenatal stress

This paper presents data suggesting a relationship between rat behavioral despair in the Porsolt test and motor lateralization in the T-maze test. In addition, experimental evidence suggests a functional coupling among dopaminergic systems, behavioral despair and motor lateralization. In the first experiment, female, not male, rats with a high level of behavioral despair showed a low level of behavioral lateralization. The inverse relationship was found in female offspring of mothers stressed during gestation. In comparison with unstressed-mother rats, the female offspring of stressed mothers showed an increase of dopamine (DA) and a decrease of dihydroxyphenylacetic acid (DOPAC) and Homovanillic (HVA) levels and of DOPAC:DA and HVA:DA indexes in the n. accumbens of the right side of the brain. No significant differences were found in the n. accumbens of the left brain. Taken together, the present data provide evidence of a relation between behavioral despair and motor lateralization, suggesting that the biological dopaminergic inervation of n. accumbens could be the basis for this functional coupling. Because the stress of gestant mothers modified these biochemical and behavioral variables, the present study also suggests that lateralization of behavior and emotion during adulthood can be modified by prenatal variables.     

Folliculogenesis in the prenatal period of human development

Quantitative analysis of the follicular formation has been performed in ovaries of 97 human embryos and fetuses (6--40-week-old). The first oocytes at the stage of diplotene appear in 11.5--12-week-old fetuses. Primordial follicles are formed around the oocyte as early as the stage of diplotene. Follicles are intensively formed after the 14th--15th week. Single primordial follicles begin to transform into the growing primary ones in 17-week-old fetuses and the process becomes active after the 19th--20th week of the development. As a rule, the oocyte reaches the stage of dictyotene only after the follicle has transformed into the primary one. By the time of birth most of oocytes are enclosed by the primary, and in less number--by the primordial follicles. The number of secondary and tertiary cavitary follicles is small. The formation rate of follicles with binuclear oocytes and that of polyoocytic follicles is stated. The data on quantitative analysis of oocyte degeneration at the stages of diplotene and dictyotene are presented.     

Rat behavioral thermoregulation integrates with nonshivering thermogenesis during postnatal development.

Rat pups are capable of behavioral thermoregulation, both in the nest and on a thermocline, as early as the 1st week of postnatal life, and these pups can also produce heat metabolically without shivering. The rat pup's primary source of nonshivering thermogenesis is the sympathetically mediated metabolism of brown adipose tissue (BAT). BAT is well formed in newborns and functions shortly after birth. While infant behavioral thermoregulation and BAT thermogenesis have been extensively studied, little is known about the extent to which thermoregulatory behavior can be influenced by BAT thermogenesis. In the present study, 2-, 7-, and 14-day-old pups were observed on a thermal gradient following pharmacological stimulation or inhibition of BAT thermogenesis, and their thermal preferences were quantified. The authors found that 7- and 14-day-old pups treated with norepinephrine (NE), which increases BAT thermogenesis, preferred cooler portions of the gradient than saline-treated controls, whereas 2-day-olds failed to show a similar NE-induced behavioral adjustment. These findings indicate that the ability to adjust thermoregulatory behavior to compensate for enhanced metabolic thermogenesis develops during the 1st week of postnatal life. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Endocrine and behavioral effects of airpuff-startle in rats

Computerized tests of neurobehavioral function are frequently administered in neurotoxicological studies with little attention given to the optical properties of test stimuli or to the vision of subjects. Yet many test stimuli are small or briefly presented, and test endpoints often involve short reaction times. Stimulus detection and reaction time are known to be strongly dependent upon stimulus luminance, contrast, and size, as well as on the subject's visual abilities. The current study assessed the influence of visual contrast sensitivity on Neurobehavioral Evaluation System 2 (NES2) test results in three data sets. Analyses indicated that vision was associated with up to 24% of the variance (Hand Eye Coordination test) in NES2 scores, even when visual acuity was normal, and that vision often influenced the significance of group differences. It is suggested that researchers measure the luminance, contrast, and size of test stimuli, the distance from the subject's eyes to the monitor, and the subject's visual contrast sensitivity. The measurement and control of stimulus parameters and the inclusion of visual function scores in analysis models could reduce the variability among computerized test scores both within and between studies. Models that assess the influence of vision on computerized test results may help to identify the CNS domains and specialized functions adversely affected by neurotoxicant exposures.     

Voluntary exercise influences behavioral development in rats exposed to alcohol during the neonatal brain growth spurt.

Children exposed to alcohol prenatally may suffer from severe brain damage, expressed as a variety of behavioral problems, including hyperactivity and learning deficits. There is a critical need to identify effective treatments for fetal alcohol effects. Physical exercise enhances cognitive ability and increases neurogenesis in the hippocampus, a brain area important for learning and memory. Thus, the present study examined whether physical exercise might reduce the severity of alcohol-induced behavioral alterations. Sprague-Dawley rats were intubated with 5.25 g/kg/day ethanol during the third trimester equivalent (postnatal days [PDs] 4-9). Intubated sham control and nontreated controls were included. From PD 21 to PD 51, half of the subjects were given access to running wheels. On PD 52, subjects were tested on the Morris water maze, and on PD 60, open field activity levels were measured. Morris maze performance was significantly impaired among ethanol-exposed subjects; exercise significantly improved performance of all groups. Similarly, ethanol-exposed subjects were overactive in the open field, an effect attenuated with exercise. In sum, these data suggest that exercise may increase neuronal plasticity not only in controls, but also in subjects exposed to alcohol during development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The importance of nonshared (E?) environmental influences in behavioral development.

Defines "nonshared" influences as those that make siblings different from one another and suggests that such influences account for any substantial variation in personality, cognition, and psychopathology. With the belief that this is especially true of environmental causes of variation, different types of nonshared environmental influence (NEI) are considered: accidental factors, sibling interaction, family structure, differential parental treatment, and extrafamilial networks. Though the preliminary evidence suggests that NEI's may be difficult to identify and that these influences may be relatively trait specific, a fuller understanding of NEI's will be possible only when research includes more than 1 member of a family. (42 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Developing behavioral objectives for perioperative staff development

Behavioral objectives (i.e., clear statements that describe intended instructional outcomes) are a crucial component of educational planning for perioperative staff development. Properly written objectives promote positive learning outcomes such as increased motivation, better retention of information, and improved instructional accountability. This article describes the advantages of using behavioral objectives, gives a historical perspective of their development, presents a practical "how-to" approach to formulating them, and delineates their link to the selection of appropriate evaluation methods.     

Role of the prenatal environment in the development of obesity

Establishing that prenatal life is a critical or sensitive period for the development of obesity may focus basic research and clinical prevention efforts on this period. This review summarizes evidence that the intrauterine environment influences the risk of later obesity and considers the mechanisms by which this may occur. The association between birth weight and adult weight suggests that there are enduring effects of the intrauterine environment on later obesity risk. We examine whether the maternal factors of diabetes, obesity, and pregnancy weight gain alter the intrauterine environment and thereby increase the risk of later obesity in the offspring. Of these maternal factors, evidence is strongest for the role of maternal diabetes. No single mechanism explains how these maternal factors could change the intrauterine environment to increase obesity risk. However, all potential mechanisms involve an altered transfer of metabolic substrates between mother and fetus, which may influence the developing structure or function of the organs involved in energy metabolism.     

Effect of prenatal haloperidol administration on anxiety patterns in rats

Haloperidol (0.1 mg/kg, i.p.) treatment was given from day 12 to 20 of gestation to pregnant rats, this being the critical period for neural development in this species. The pups born were subjected to open-field exploratory behaviour, tunnel-board exploratory behaviour, elevated zero-maze and elevated plus maze behaviour tests at 7-8 weeks of age. The results indicate that prenatal haloperidol treatment induces a significant increase in open-field ambulations and rearings, decrease in scratching and licking/washing behaviours whereas grooming and faecal droppings remain unchanged. Significantly reduced activity in the centre and increased activity in the periphery of the tunnel board was noted. These suggest presence of anxiety in these animals. Significant anxiogenic behavioural patterns were also observed on elevated zero-maze and plus-maze in the prenatally haloperidol treated offsprings. The results suggest that prenatal exposure of haloperidol leaves a lasting effect on offsprings resulting in hyper-emotional responsiveness and anxiety state.     

The behavioral development of Korean children in institutional care and international adoptive families.

In this study, the authors compared the behavioral development of 4- to 8-year-old South Korean children placed in institutional care (n = 230) or adopted internationally (n = 382), with age of entry, parental status, reason for institutionalization, and postinstitutionalization parental contact as risk factors for institutionalized children. There was a placement effect of adoption and support for age of entry and parental status as risk factors. Relinquished children institutionalized before age 2 fared the poorest across groups. Children institutionalized after age 2 with deceased/unknown parents fared best among institutionalized children. Institutionalization due to family disruption was a risk for relinquished children only, whereas parental contact did not increase the risk for behavioral problems. The unique sample population and other limitations are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)