Maternal voluntary physical activity attenuates delayed neurodevelopment in malnourished rats.

NEW FINDINGS: What is the central question of this study? In the present study, a reproducible model of maternal voluntary physical activity was developed to evaluate the adaptive response of physical activity by attenuating the effects of maternal undernutrition on physical features, reflex ontogeny and growth trajectory of offspring during development. What is the main finding and its importance? Maternal physical activity may induce neuronal maturation of sensorimotor connections impacting on the patterns of locomotor activity in malnourished offspring. Thus, physical activity should be considered as a therapeutic means of countering the effects of maternal undernutrition, by providing a useful strategy for enhancing the neuronal activity of children born to mothers who experience a restricted diet during pregnancy. This study evaluated the effects of maternal voluntary physical activity during pregnancy and lactation on somatic growth (SG), reflex ontogeny (RO) and locomotor activity (LA) of rats whose mothers were protein restricted. Virgin female Wistar rats were divided into the following six groups: control, normal protein (C-NP, n = 4); control, low protein (C-LP, n = 4); inactive, normal protein (I-NP, n = 8); inactive, low protein (I-LP, n = 7); very active, normal protein (VA-NP, n = 8); and very active, low protein (VA-LP, n = 6). Voluntary physical activity was recorded daily in dams. The LP groups were fed an 8% casein diet, whereas control groups were fed a 17% casein diet during pregnancy and lactation. Offspring were evaluated in terms of SG (body weight and length, latero-lateral skull axis and anteroposterior head axis) and RO (palmar grasp, righting, free-fall righting, negative geotaxis, cliff avoidance, auditory startle response and vibrissa placing). The LA was evaluated at 23, 45 and 60 days old in the open field. Voluntary physical activity was reduced during pregnancy and lactation independent of the maternal diet. Pups from LP dams showed delayed SG, reflex maturation and patterns of LA when compared with control pups. The C-LP and I-LP pups showed a delayed SG, RO and LA. Pups from VA-LP mothers showed no delay in SG and RO and presented a faster development of patterns of LA. Maternal voluntary physical activity attenuated the effects of LP diet on indicators of neurodevelopment and patterns of LA of offspring.

Malnutrition in the first year of life and personality at age 40.

BACKGROUND: Early childhood malnutrition is associated with cognitive and behavioral impairment during childhood and adolescence, but studies in adulthood are limited. METHODS: Using the NEO-PI-R personality inventory, we compared personality profiles at 37-43 years of age (M 40.3 years, SD 1.9) of Barbadian adults who had experienced moderate-to-severe protein-energy malnutrition (PEM) in the first year of life (n = 77) with healthy controls, who were former classmates of the index cases and were matched for age, gender, and handedness in childhood (n = 57). The previously malnourished participants had been rehabilitated, with good health and nutrition documented up to 12 years of age, and study participants were followed longitudinally from childhood to 40 years. Group comparisons were adjusted for childhood and adolescent standard of living, with and without correcting for IQ. RESULTS: At the broad domain or factor level, previously malnourished participants had higher scores on Neuroticism and lower scores on Extraversion, Openness, Agreeableness, and Conscientiousness than did the healthy controls. At the subdomain or facet level, previously malnourished participants reported more anxiety, vulnerability, shyness and lowered sociability, less intellectual curiosity, greater suspiciousness of others, a more egocentric than altruistic orientation, and a lowered sense of efficacy or competence. CONCLUSIONS: Malnutrition limited to the first year of life with good health and nutrition documented up to 12 years of age is associated with a significant overrepresentation of adult personality trait scores outside of the average range. This outcome has important implications for a variety of important life and mental health outcomes.

Infant malnutrition is associated with persisting attention deficits in middle adulthood.

Infantile malnutrition is known to be associated with cognitive and behavioral impairment during childhood and adolescence. Data pertaining to longer-term effects on behavioral outcomes in adulthood are limited. In this study, we report associations between infantile malnutrition and attention problems in adults at midlife. Attention problems were assessed by the Conners Adult ADHD Rating Scales (CAARS) and the Conners Continuous Performance Test (CPT) in 145 Barbadian adults (aged 37-43 y) who had been followed longitudinally since childhood. Previously malnourished participants (n = 80) had experienced moderate to severe protein-energy malnutrition in the first year of life and were successfully rehabilitated thereafter. They were compared with healthy adults (n = 65) who were former classmates of the index cases and who had been matched for age, sex, and handedness in childhood. Multiple regression analyses showed persisting effects of childhood malnutrition on both the CAARS and the CPT, independent of effects of household standard of living assessed in childhood. The malnutrition effect on the CAARS ratings was independent of IQ, whereas this effect was attenuated for the CPT after adjustment for IQ. Teacher-reported attention problems in childhood predicted attention problems in adulthood, indicating continuity over the life span. Infantile malnutrition may have long-term effects on attentional processes nearly 40 y after the episode, even with excellent long-term nutritional rehabilitation and independent of socioeconomic conditions in childhood and adolescence. This finding has major public health implications for populations exposed to early childhood malnutrition.

Cognitive impairment as a mediator in the developmental pathway from infant malnutrition to adolescent depressive symptoms in Barbadian youth.

OBJECTIVE: Depressive symptoms are elevated in adolescents who experienced significant malnutrition early in life. Early malnutrition can also have a significant impact on cognitive functioning, presumably because of the adverse impact of the malnutrition on the very young brain. In the context of a developmental cascade model, we tested the hypothesis that the association between early malnutrition and adolescent depressive symptoms is mediated by the cognitive impairment that ensues from the malnutrition. METHODS: We evaluated Barbadian youth (N = 57) hospitalized for moderate to severe protein-energy malnutrition in the first year of life and healthy controls (N = 60) longitudinally. The primary hypothesis was tested by multiple regression models. RESULTS: After adjusting for covariates, early malnutrition predicted both cognitive functioning in childhood (IQ, p < .001; attention problems, p < .01; Common Entrance Examination, p < .01; and adolescent depressive symptoms, p < .05). Childhood cognitive functioning mediated the association between early malnutrition and depressive symptoms in adolescence (p < .001). Maternal depressive symptoms were a significant but independent predictor of adolescent depressive symptoms (p < .05). CONCLUSIONS: Cognitive compromise in childhood accounts indirectly for elevated depressive symptoms in previously malnourished adolescents, consistent with a developmental cascade model. The direct link between malnutrition and depressive symptoms in adolescence is small.

Anxiety-like behavior in weanling and young adult male and female malnourished rats.

The present study determined whether protein-calorie malnutrition alters anxiety-like behavior in weanling and young adult, male and female malnourished rats. On the day of birth, litters of Wistar rats were divided into Control (C) and Malnutrition (M) groups. In the C group, litters were fed by dams receiving ad libitum lab chow, whereas in the M group, litters were fed by dams receiving 40% of the total amount of the diet offered to dams in the C group. After weaning (PND21) until PND50, animals received the same food as theirs mothers (i.e., ad libitum access in the C group and 40% of the C group food in the M group). On PND21 and PND50, independent C (male [CM] and female [CF]) and M (male [MM] and female [MF]) groups were exposed to the elevated T-maze. The time taken to withdraw four paws from this arm was recorded (baseline latency [BL]). The same measurement was repeated twice at 30s intervals (avoidance trial 1 [AT1] and avoidance 2 [AT2]). The cutoff time in each trial was 300s. ANOVA indicated a four-way age×diet×sex×trials interaction. Post hoc comparisons revealed that PND50 rats had a lower BL and AT1 latency compared with PND21 rats. Training increased both AT1 and AT2 latencies compared with BL in both the CM and CF groups. Weanling malnourished rats exhibited reduced anxiety-like behavior and young adult male rats presented less anxiety-like behavior than young adult female rats in this experimental model.

Early childhood malnutrition predicts depressive symptoms at ages 11-17.

BACKGROUND: We examined the prevalence of depressive symptoms in Barbadian youth with histories of infantile malnutrition and in a healthy comparison group and the extent to which the effect of malnutrition was mediated/moderated by maternal depression. METHODS: Depressive symptoms were assessed using a 20-item scale administered to youths (11-17 years of age) who had experienced an episode of protein-energy malnutrition (marasmus or kwashiorkor) during the first year of life and in a comparison group of healthy youths without a history of malnutrition. Their mothers completed the same questionnaire on the same test on three occasions when their children were 5-17 years of age at 2-5-year intervals. RESULTS: The prevalence of depressive symptoms was elevated among previously malnourished youth relative to healthy comparison children (p < .001). When youth depression scores were subjected to a longitudinal multiple regression analysis, adjusting for the effect of maternal depressive symptoms, significant effects due to the history of early childhood malnutrition remained and were not discernibly attenuated from an unadjusted analysis. We also found significant independent effects of maternal depressive symptoms on youth depressive symptoms. CONCLUSION: Early childhood malnutrition contributed independently to depressive symptoms in youths who experienced a significant episode of malnutrition in the first year of life. This relationship was not mediated or moderated by the effects of maternal depression. Whether the later vulnerability to depression is a direct effect of the episode of malnutrition and related conditions early in life or whether it is mediated by the more proximal neurobehavioral effects of the malnutrition remains to be determined.

Some indicators of nutritional status are associated with activity and exploration in infants at risk for vitamin and mineral deficiencies.

Severe malnutrition, both protein-energy and micronutrient deficiency, results in decreased activity, but the results regarding mild-to-moderate malnutrition are equivocal. Our objective in this investigation was to describe the activity and exploratory behavior of Mexican infants and describe the relationship among nutritional status, activity, and exploration in this population at high risk for mild-to-moderate micronutrient deficiency, but at low risk for severe malnutrition. The participants were infants, 4-12 mo old, of low socioeconomic status from 3 states in southern Mexico. We measured anthropometrics using standard techniques. We measured hemoglobin (Hb) concentration in the field and adjusted values for altitude before analysis. We measured activity and exploration by direct observation during 15 min of individual play in a novel environment. Cluster analysis generated mutually exclusive activity clusters and exploration clusters based on patterns of bodily movement and exploratory behavior, respectively. We categorized the clusters as higher or lower activity or higher or lower exploration. A higher Hb concentration and height-for-age Z-score (HAZ) significantly increased the odds of being in the high-activity cluster. Iron deficiency, stunting, and wasting significantly decreased the odds of being in the high-activity cluster. Higher HAZ and weight-for-age Z-score significantly increased the odds of being in a higher exploration cluster. In Mexican infants at risk for mild-to-moderate micronutrient deficiency but at low risk of severe malnutrition, some indicators of nutritional status were related to increased activity and exploration.

Differential response to gepirone but not to chlordiazepoxide in malnourished rats subjected to learned helplessness

The learned helplessness (LH) paradigm is characterized by learning deficits resulting from inescapable events. The aims of the present study were to determine if protein-calorie malnutrition (PCM) alters learning deficits induced by LH and if the neurochemical changes induced by malnutrition alter the reactivity to treatment with GABA-ergic and serotonergic drugs during LH. Well-nourished (W) and PCM Wistar rats (61 days old) were exposed or not to inescapable shocks (IS) and treated with gepirone (GEP, 0.0-7.5 mg/kg, intraperitoneally, N = 128) or chlordiazepoxide (0.0-7.5 mg/kg, intraperitoneally, N = 128) 72 h later, 30 min before the test session (30 trials of escape learning). The results showed that rats exposed to IS had higher escape latency than non-exposed rats (12.6 ± 2.2 vs 4.4 ± 0.8 s) and that malnutrition increased learning impairment produced by LH. GEP increased the escape latency of W animals exposed or non-exposed to IS, but did not affect the response of PCM animals, while chlordiazepoxide reduced the escape deficit of both W and PCM rats. The data suggest that PCM animals were more sensitive to the impairment produced by LH and that PCM led to neurochemical changes in the serotonergic system, resulting in hyporeactivity to the anxiogenic effects of GEP in the LH paradigm.

Differential response to gepirone but not to chlordiazepoxide in malnourished rats subjected to learned helplessness.

The learned helplessness (LH) paradigm is characterized by learning deficits resulting from inescapable events. The aims of the present study were to determine if protein-calorie malnutrition (PCM) alters learning deficits induced by LH and if the neurochemical changes induced by malnutrition alter the reactivity to treatment with GABA-ergic and serotonergic drugs during LH. Well-nourished (W) and PCM Wistar rats (61 days old) were exposed or not to inescapable shocks (IS) and treated with gepirone (GEP, 0.0-7.5 mg/kg, intraperitoneally, N = 128) or chlordiazepoxide (0.0-7.5 mg/kg, intraperitoneally, N = 128) 72 h later, 30 min before the test session (30 trials of escape learning). The results showed that rats exposed to IS had higher escape latency than non-exposed rats (12.6 +/- 2.2 vs 4.4 +/- 0.8 s) and that malnutrition increased learning impairment produced by LH. GEP increased the escape latency of W animals exposed or non-exposed to IS, but did not affect the response of PCM animals, while chlordiazepoxide reduced the escape deficit of both W and PCM rats. The data suggest that PCM animals were more sensitive to the impairment produced by LH and that PCM led to neurochemical changes in the serotonergic system, resulting in hyporeactivity to the anxiogenic effects of GEP in the LH paradigm.

Early postnatal protein malnutrition causes resistance to the anxiolytic effects of diazepam as assessed by the fear-potentiated startle test.

Given that protein malnutrition induces structural, neurochemical and functional changes in the CNS, the present study aimed to investigate the effects of different early periods of protein malnutrition on the behavior and reactivity to diazepam (DZ) in a model of anxiety: the fear-potentiated startle (FPS). Male Wistar rats (n = 110) from well-nourished (16 %-protein) or malnourished (6%-protein) litters were distributed in five different groups: W (well-nourished), M7 (malnourished for 7-days, since day 0), M14 (14-days), M21 (21-days) and M28 (28-days). The results obtained in FPS revealed that malnourished-animals acquired the startle response, irrespective of the time they were exposed to the diet. Besides, DZ reduced the startle amplitude in the noise-alone and light-noise trials. The data concerning the total freezing time showed that the expression of this response was affected by malnutrition and varied in accordance with the findings of previous studies in which malnutrition procedures was imposed for long periods (more than 50 days). Therefore, we suggest that early protein malnutrition: (a) did not produce deficits in the associative learning process of these animals in the FPS, and (b) decreased freezing time in the FPS and produce hyporeactivity to the effects of DZ in rats malnourished for 21 days or more, indicating alterations in the GABAergic neurotransmitter system.

[Multivariate study of the Open Field Drink Test using undernourished rats and desipramine as an antipanic drug]. / Estudio multivariado del test de bebida en campo abierto con ratas hiponutridas y desipramina como droga antipánico.

Approach-avoidance animal models are useful as initial screens for drugs affecting anxiety, but the components of anxiety assessed by these models remain poorly defined. Complex models of evaluation allow more complete inferences than those which are obtained when only one behavior is evaluated. Previous studies demonstrate that the tricyclic-antidepressant desipramine exerts a selective anticonflict effect on adult rats submitted to a protein deprivation schedule at perinatal age, in parameters of spontaneous behavior (elevated plus-maze) and conditioned intake (Geller Seifter). These deprived rats show alterations in noradrenergic neurotransmission that resembled the generalized activation of noradrenergic system displayed by patients suffering from panic attacks. The desipramine anticonflict activity was evaluated by a test of ethological conflict: the Open Field Drink Test, without discarding any behavior a priori under a multivaried approach. This approach has not been considered in previous studies with the open field and antipanic drugs. Considering the four variables selected by factorial analysis, desipramine (10 mg/kg/day) administered IP during just 7 days produced a significant diet x drug interaction which was consistent with previous studies. That interaction was independent of the effects of both treatments on weight or intake and was expressed, on deprived rats, as a decrease in all the behaviors, except for the time of drinking, with respect to the control rats, which displayed, in general, a decrease in all the behaviors except for the frequency of grooming.

Early postnatal protein malnutrition changes the development of social play in rats.

Early protein malnutrition produces structural and functional alterations in the brain and changes the organism-environment interactions. Rats from 26 to 76 days of age were used to study the effects of early postnatal protein malnutrition on the development of social play. During lactation phase the litters were fed diet containing 16% protein (well-nourished) or 6% protein (malnourished). From weaning to the end of behavioral tests well-nourished animals were fed a commercial lab chow diet (well-nourished--W) and the malnourished rats were divided into 2 groups: one was maintained on 6% protein diet (malnourished--M) and the other was fed a commercial lab chow diet (previously malnourished--PM). Pairs of male rats of same diet conditions were tested, at different ages, for three consecutive days. During sessions the following behaviors were recorded: pinning, wrestling, walk-over and rear. The frequency of wrestling and walk-over was significantly higher in malnourished as compared to well-nourished animals (p<0.05). Early protein malnutrition also changed the ontogeny of play behaviors (pinning and wrestling) with developmental retards in M and PM as compared with W animals, especially at 46 and 56 days of age. These results suggest that early protein malnutrition can affect the development of neural mechanisms underlying social play in rats.

Increased locomotor response to amphetamine, but not other psychostimulants, in adult mice submitted to a low-protein diet.

Protein malnutrition results in a variety of brain dysfunctions, ultimately affecting cognitive functions. The effects of protein malnutrition in brain response to psychostimulants have been less studied in adult animals. We therefore aimed to study the response to psychoactive drugs on the locomotor activity (a behavior paradigm) of adult protein malnourished mice. Two-month-old mice were divided in two groups: (a) low-protein group (LP), which received 6% of protein diet, and (b) a control group that received a 25% of protein diet. After 3 months, they were tested for locomotor activity after an i.p. injection of one of psychoactive drugs: D-amphetamine (5.0 mg/kg), apomorphine (2.0 mg/kg), dizocilpine (0.25 mg/kg), or caffeine (30 mg/kg). Mice submitted to the LP diet presented prolonged induction of hyperlocomotion caused by amphetamine (about 350% between 90 and 180 min post drug injection as compared with well-nourished mice, p<0.01) but presented unaltered response to apomorphine, caffeine, and dizocilpine. These data point to altered catecholamine metabolism induced by protein restriction in adult mice. The results are discussed based on previous works, presenting theoretical hypotheses about the possible mechanisms involved in the present findings.

Head size and intelligence, learning, nutritional status and brain development. Head, IQ, learning, nutrition and brain.

This multifactorial study investigates the interrelationships between head circumference (HC) and intellectual quotient (IQ), learning, nutritional status and brain development in Chilean school-age children graduating from high school, of both sexes and with high and low IQ and socio-economic strata (SES). The sample consisted of 96 right-handed healthy students (mean age 18.0 +/- 0.9 years) born at term. HC was measured both in the children and their parents and was expressed as Z-score (Z-HC). In children, IQ was determined by means of the Wechsler Intelligence Scale for Adults-Revised (WAIS-R), scholastic achievement (SA) through the standard Spanish language and mathematics tests and the academic aptitude test (AAT) score, nutritional status was assessed through anthropometric indicators, brain development was determined by magnetic resonance imaging (MRI) and SES applying the Graffar modified method. Results showed that microcephalic children (Z-HC < or = 2 S.D.) had significantly lower values mainly for brain volume (BV), parental Z-HC, IQ, SA, AAT, birth length (BL) and a significantly higher incidence of undernutrition in the first year of life compared with their macrocephalic peers (Z-HC > 2S.D.). Multiple regression analysis revealed that BV, parental Z-HC and BL were the independent variables with the greatest explanatory power for child's Z-HC variance (r(2) = 0.727). These findings confirm the hypothesis formulated in this study: (1) independently of age, sex and SES, brain parameters, parental HC and prenatal nutritional indicators are the most important independent variables that determine HC and (2) microcephalic children present multiple disorders not only related to BV but also to IQ, SA and nutritional background.

Early postnatal protein malnutrition affects learning and memory in the distal but not in the proximal cue version of the Morris water maze.

Learning and memory of early postnatal protein malnourished rats were investigated in the Morris water maze. During the lactation period (21 days) each litter (mother plus six male and two female pups) was provided with 16% (well-nourished) or 6% (malnourished) protein diets. After weaning, rats remained on the same diet until 49 days of age. From day 50 on all animals were fed a commercial lab chow. Experiments started on day 70. In experiment I (proximal cue version) the animals were trained to escape from water to a visible platform (3 cm above the water level) in six trials daily for four consecutive days, completing 24 trials. In experiment II (distal cue version) the animals were trained to escape from water to a submerged platform using the same procedure as in experiment II. After the 24th trial, the platform was removed and the animals were submitted to a 60-s trial (probe trial). Seven and twenty-eight days after training, the retention test was conducted in one 180-s trial. The results showed no impairment of the learning or memory of malnourished animals tested in the proximal cue version but an increased latency and distance traveled to find the submerged platform in the distal cue version of the procedure. In the distal cue version the malnourished animals also showed increased latency to find the platform 7 and 28 days after the test training. No difference due to diet was found in the probe trial test indicating that, once the task is acquired, malnourished rats can manage extra-maze cues as easily as well-nourished rats. It is suggested that the present results can be due to alterations produced by protein malnutrition in the hippocampal formation or also to reflect the higher emotionality of rats following early malnutrition, specially considering the fact that postnatally malnourished animals are more reactive to unpleasant or aversive stimuli as cold water.

Postnatal protein malnutrition affects play behavior and other social interactions in juvenile rats.

The effects of postnatal protein malnutrition on juvenile social behaviors were investigated in male and female Wistar rats. During the lactation period (21 days), each litter (six male and two female pups) was provided with 16% (control) or 6% (low protein) casein diets. At weaning, the control group (W) continued to receive the 16% protein diet and the malnourished group was divided into two groups: one continuing to receive a 6% protein diet (malnourished group - M) and the other shifted to a 16% protein diet (previously malnourished group - PM). These conditions lasted until 38 days of age when the behavioral tests ended. To assess social interaction, pairs of rats of the same nutritional condition and same gender were placed in a familiar arena for 3 consecutive days. Playful social behavior (pin), nonplayful social behavior (anogenital sniff, walk-over, side-mount and allogroom) and nonsocial behavior (rear) were recorded in three 10-min sessions. Postnatal protein malnutrition significantly decreased playful social behavior, nonsocial behavior (rear) and nonplayful social behaviors such as side-mount and walk-over. Anogenital sniff and allogroom were increased by early malnutrition. Nutritional rehabilitation from weaning reversed the changes produced by protein malnutrition in nonplayful (side-mount, walk-over, anogenital sniff and allogroom) and nonsocial behaviors (rear) but increased playful social behavior (pin). Gender effects were observed only on side-mount (higher incidence in males) and walk-over (higher incidence in females) indicating that playful behavior and nonsocial behavior were not affected by sex. The present results suggest that behavioral differences described in adulthood may result from changes in social behaviors of juvenile rats induced by early protein malnutrition.

Behaviour and development of stunted and nonstunted Jamaican children.

In order to examine the mechanism whereby stunted children have poor developmental levels, we compared the behaviour of stunted (N = 78) and nonstunted (N = 26) children aged 12 to 24 months, and examined the relationship of their behaviour to their developmental levels. The effect of nutritional supplementation with or without psychosocial stimulation on the stunted children's behaviour was also examined. The children were observed at home during 4 days over a period of 6 months. The stunted children showed significantly more apathy, and less enthusiasm and variety in exploring, were less happy and more fussy. Caretakers' vocalisations to them were less warm or instructive. Stunted children's activity level, exploratory and happy behaviours were predictive of change in developmental levels measured on the Griffiths Scales, from enrolment to 12 and 24 months later. Supplementation predicted mental age at 12 and 24 months after enrolment, however, it had no significant effect on behaviour.

Behaviour and development of stunted and nonstunted Jamaican children

In order to examine the mechanism whereby stunted children have poor developmental levels, we compared the behaviour of stunted (N = 78) and nonstunted (N = 26) children aged 12 to 24 months, and examined the relationship of their behaviour to their developmental levels. The effect of nutritional supplementation with or without psychosocial stimulation on the stunted children's behaviour was also examined. The children were observed at home during 4 days over a period of 6 months. The children significantly showed more apathy, and less enthusiasm and variety in exploring, were less happy and more fussy. Caretakers' vocalisations to them were less warm or instructive. Stunted children's activity level, exploratory and happy behaviours were predictive of change in developmental levels measured on the Griffiths Scales, from enrolment to 12 and 24 months later. Supplementation predicted mental age at 12 and 24 months later enrolment, however, it had no significant effect on behaviour (Au)

Effect of perinatal malnutrition on the inactive behavior induced by long-term shock and conditioned analgesia.

Inactive behavior in response to long-term inescapable foot shock (IS) and conditioned analgesia were evaluated in adult rats perinatally undernourished. During the IS session, control rats exhibited first a period of vigorous activity and then inactive behavior, during which they accepted the shock more passively. Moreover, when these same animals were subsequently placed in the environment associated with shock application, they showed an increase in the paw lick latency. Conversely, in malnourished rats, this IS schedule induced lower behavioral inactivity and rats failed to develop conditioned analgesia. When undernourished rats were injected with morphine (MOR) before IS exposure, it was observed that both phenomena--inactivity during shock and analgesia conditioned by submission to the shock context--were normalized. A possible alteration in the activation of an opiate process implicated in the stress response in early undernourished rats is suggested.