Family factors affecting child development.
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In a large, geographically defined population of children a number of family factors in addition to social class, determined by the father's occupation, were recorded by health visitors and school nurses with routine responsibility for these children. The quality of the children in normal schools was assessed in terms of nonverbal IQ and height at the ages of 5 and 10 years, and of behavior as reported by the teacher at the age of 10 years. By analysis of variance the sum of the independent effects of the other family factors greatly outweighed that of occupational social class, except in the case of the IQ at 10 years. The most important of the other family factors was the quality of the mother's care of her child during the first 3 years of life. (+info)
Differential regulation of glucocorticoid receptor messenger RNA (GR-mRNA) by maternal deprivation in immature rat hypothalamus and limbic regions.
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Maternal deprivation (MDep) of neonatal rats significantly influences the hypothalamic-pituitary-adrenal (HPA) axis. This study hypothesized that GR-mRNA modulation constituted an early, critical mechanism for the acute effects of MDep on neuroendocrine stress-responses. GR-mRNA hybridization signal in hippocampal CA1, hypothalamic paraventricular nucleus (PVN) and frontal cortex was significantly reduced immediately following 24 h MDep. In amygdala, cingulate cortex, PVN and CA1, apparent gender-dependent MDep effects on GR-mRNA expression were observed, without significant differences in absolute levels. Thus, rapid, region-specific MDep effects on GR-mRNA expression in HPA-regulating areas are shown, consistent with involvement of GR-expression in mechanisms of MDep influence on HPA tone. (+info)
The long-term effects of maternal deprivation depend on the genetic background.
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The neurodevelopmental hypothesis of schizophrenia has led to a series of new animal models in which the long term consequences of early manipulations are investigated. We have recently shown that a single 24-hr period of maternal deprivation (at postnatal day (pnd) 9) increases apomorphine susceptibility and decreases prepulse inhibition in Wistar rats, viz. phenomena also seen in schizophrenic patients. In the present paper, we investigated whether the effects of maternal deprivation were dependent on a specific genetic background, by using different rat strains (Fischer 344 and Lewis) that differ in the Hypothalamus-Pituitary-Adrenal axis and in dopaminergic sensitivity. The data show that in Wistar rats, basal startle amplitude was not affected by maternal deprivation, but prepulse inhibition was reduced, and apomorphine susceptibility enhanced. In Fischer 344 rats on the other hand, neither basal startle amplitude, nor prepulse inhibition were affected, but apomorphine susceptibility was reduced. In Lewis rats, maternal deprivation significantly reduced basal startle amplitude, but did not affect prepulse inhibition or apomorphine susceptibility. The differential response to maternal deprivation can best be explained by differences in baseline dopamine sensitivity between the rat strains. Since a reduced prepulse inhibition and an enhanced susceptibility to apomorphine is also seen in schizophrenic patients, the data indicate that maternally deprived Wistar rats may represent an interesting developmental model for (aspects of) schizophrenia. (+info)
Parental deprivation induces N-methyl-D-aspartate-receptor upregulation in limbic brain areas of Octodon degus: protective role of the maternal call.
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An optimal coordination between parents and their offspring involves a sequence of reciprocal behaviors to ensure the adequate care of the young, which is critical for a healthy physical, emotional, and social development. Parental deprivation, particularly an impaired child-mother attachment, induces lasting changes in emotional as well as in cognitive capacities in later life. We assessed in the South American precocial species, Octodon degus, whether alterations of glutamatergic function of the limbic system induced by parental deprivation may be a neural correlate for such behavioral changes. Further, we analyzed whether the mother's voice can protect from separation-induced changes of brain function. Changes of N-methyl-D-aspartate (NMDA) receptor expression were examined in the following three groups of 2-week-old Octodon degus pups: (I) control animals who remained undisturbed with the family; (II) animals who were repeatedly separated from the family and individually placed in an unfamiliar environment for behavioral analysis (open field); and (III) animals who were treated like the group described under (II) but were presented with maternal vocalizations during separation. Relative to those in the control group I, the animals in group II showed an upregulation of NMDA receptor density in the (a) anterior cingulate, prelimbic, infralimbic, and anterior insular cortices; (b) CA1/stratum radiatum; (c) CA1/stratum lacunosum moleculare and CA3/stratum radiatum; and (d) in the basomedial amygdaloid nucleus. Presentation of the maternal call during the separation period (group III) suppressed the separation-induced NMDA receptor upregulation in all regions. The results demonstrate that early life events can influence the expression of transmitter receptors and that maternal behavior, acting to control the pup's socio-emotional environment, is a key factor for regulating such developmental events. (+info)
Selective blockade of neurokinin-2 receptors produces antidepressant-like effects associated with reduced corticotropin-releasing factor function.
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The present study investigated the effects of the selective neurokinin-2 (NK2) receptor antagonist SR48968 in behavioral, electrophysiological, and biochemical tests sensitive to the action of prototypical antidepressants (fluoxetine, imipramine) or to corticotropin-releasing factor (CRF) receptor antagonists, which have been proposed recently as potential antidepressants. Results showed that SR48968 (0.3-10 mg/kg i.p.) produced antidepressant-like activity because it reduced immobility in the forced swimming test in both mice and rats, and decreased the amount of maternal separation-induced vocalizations in guinea pig pups. This latter effect appears to involve a reduction of stress-induced substance P release because SR48968 reduced the separation-induced increase in the number of neurons displaying neurokinin-1 receptor internalization in the amygdala. Furthermore, SR48968 increased the expression of the cAMP response-element binding protein mRNA in the rat hippocampus after repeated (1 mg/kg i.p., 21 days), but not acute administration. Finally, neuronal firing of the locus coeruleus (LC) and noradrenergic (NE) release in the prefrontal cortex both elicited by an uncontrollable stressor or an intraventricular administration of CRF were reduced by SR48968 (0.3-1 mg/kg i.p.). The finding that SR48968 (1 mg/kg i.p.) blocked the cortical release of NE induced by an intra-LC infusion of the preferential NK2 receptor agonist neurokinin A suggested the presence of NK2 receptors in this latter region. Importantly, SR48965 (1-10 mg/kg i.p.), the optical antipode of SR48968, which is devoid of affinity for the NK2 receptor, was inactive in all the models used. These data suggest that NK2 receptor blockade may constitute a novel mechanism in the treatment of depression and CRF-related disorders. (+info)
Fluoxetine enhances cell proliferation and prevents apoptosis in dentate gyrus of maternally separated rats.
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The mother-infant relationship is an instinctive phenomenon, and loss of maternal care in early life influences neonatal development, behavior and physiologic responses.(1,2) Furthermore, the early loss may affect the vulnerability of the infant to neuropsychiatric disorders, such as childhood anxiety disorders, personality disorders and depression, over its lifespan.(3,4) Fluoxetine is prescribed worldwide for depression and is often used in the treatment of childhood mental problems related to maternal separation or loss of maternal care.(5,6) In the present study, fluoxetine was administrated to rats with maternal separation to determine its effects on neuronal development, in particular with respect to cell proliferation and apoptosis in the dentate gyrus of the hippocampus. Rat pups were separated from their mothers and socially isolated on postnatal day 14 and were treated with fluoxetine (5 mg kg(-1)) and 5-bromo-2'-deoxyuridine (BrdU) (50 mg kg(-1)) for 7 days, after which immunohistochemistry and a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining were carried out. In the pups with maternal separation treated with fluoxetine, the number of BrdU-positive cells was significantly increased and that of TUNEL-positive cells was significantly decreased in the dentate gyrus compared to pups with maternal separation that did not receive fluoxetine treatment. These findings indicate that fluoxetine affects new cell proliferation and apoptosis, and we propose that fluoxetine may be useful in the treatment of maternal separation-related diseases. (+info)
Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat.
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This study investigated the combined effect of neonatal maternal separation and acute psychological stress on pain responses in adult rats. Long-Evans dams and their male pups were reared under two conditions: 1) 180 min daily maternal separation (MS180) on postnatal days 2-14 or 2) no handling or separation (NH). At 2 mo of age, visceromotor responses to graded intensities of phasic colorectal distension (10-80 mmHg) at baseline as well as following acute 60 min water avoidance stress (WA) were significantly higher in MS180 rats. Both groups showed similar stress-induced visceral hyperalgesia in the presence of naloxone (20 mg/kg ip). MS180 rats had smaller stress-induced cutaneous analgesia in the tail-flick test compared with NH rats, with a residual naloxone-resistant component. MS180 rats showed an enhanced fecal pellet output following WA or exposure to a novel environment. These data suggest that early life events predispose adult Long-Evans rats to develop visceral hyperalgesia, reduced somatic analgesia, and increased colonic motility in response to an acute psychological stressor, mimicking the cardinal features of irritable bowel syndrome. (+info)
Effects of a non-peptide CRF antagonist (DMP696) on the behavioral and endocrine sequelae of maternal separation.
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We examined whether blockade of corticotropin-releasing factor (CRF) receptors by a non-peptide CRF antagonist (DMP696) would attenuate the stress hyper-responsiveness that occurs in response to maternal separation. In a social interaction test as well as the elevated plus maze, adult male rats, which had been maternally separated as infants, displayed more anxiety-like behavior compared with handled rats. DMP696 increased social interaction in both groups. In the elevated plus maze however, DMP696 significantly increased open arm time in the maternally separated rats but not in the handled group whereas chlordiazepoxide increased open arm time in both groups. DMP696 also appeared to block stress-induced ACTH secretion more readily in the maternally separated group compared with the handled rats. These observations suggest that CRF antagonists are particularly effective in animals that are hyper-responsive to stress and may therefore have utility in the treatment of anxiety and affective disorders where CRF has been implicated. (+info)