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Biomedical subjects

S S Almeida

Publications and source records attributed to S S Almeida.

At least 19 recordsLinked to original sources

The interaction of housing condition and acute immobilization stress on the elevated plus-maze behaviors of protein-malnourished rats.

Protein malnutrition induces structural, neurochemical and functional alterations in the central nervous system, leading to behavioral alterations. In the present study, we used the elevated plus-maze (EPM) as a measure of anxiety to evaluate the interaction between acute immobilization and housing conditions on the behavior of malnourished rats. Pups (6 males and 2 females) were fed by Wistar lactating dams receiving a 6% (undernourished) or 16% (well-nourished) protein diet. After weaning, the animals continued to receive the same diets ad libitum until 49 days of age when they started to receive a regular lab chow diet. From weaning to the end of the tests on day 70, the animals were housed under two different conditions, i.e., individual or in groups of three. On the 69th day, half of the animals were submitted to immobilization for 2 h, while the other half were undisturbed, and both groups were tested 24 h later for 5 min in the EPM. Independent of other factors, protein malnutrition increased, while immobilization and social isolation per se decreased, EPM exploration. Analysis of the interaction of diet vs immobilization vs housing conditions showed that the increased EPM exploration presented by the malnourished group was reversed by acute immobilization in animals reared in groups but not in animals reared individually. The interaction between immobilization and housing conditions suggests that living for a long time in social isolation is sufficiently stressful to reduce the responses to another anxiogenic procedure (immobilization), while living in groups prompts the animals to react to acute stress. Thus, it is suggested that housing condition can modulate the effects of an anxiogenic procedure on behavioral responses of malnourished rats in the EPM.

Animals↗

Postnatal protein malnutrition affects inhibitory avoidance and risk assessment behaviors in two models of anxiety in rats.

Protein malnutrition induces structural, neurochemical and functional alterations in the central nervous system, leading to alterations in behavioral function. In order to study the effects of early protein malnutrition on inhibitory avoidance and escape behaviors we used the elevated T-maze (ETM), while the risk assessment behaviors were evaluated by the canopy stretched attend posture (SAP) test. Rat pups were fed by lactating females receiving 16% (control) or 6% (malnourished) protein diets during the lactation period. After weaning the animals received the same diets until 49 days of age, when all animals started receiving a lab chow diet. Behavioral tests were started at 70 days of age. ETM results showed lower inhibitory avoidance in malnourished animals, without differences in escape behavior. SAP test results showed higher exploration and lower risk assessment behaviors in malnourished animals compared to control. These results suggest that malnourished animals are less anxious and/or more impulsive as measured by these two animal models and that malnutrition seems to affect differently behavioral strategies underlying fear and anxiety responses.

Animals↗

Nutrition and brain function: a multidisciplinary virtual symposium.

A few months ago, the Brazilian Society for Neuroscience and Behavior (SBNeC) promoted a "virtual symposium" (by Internet, under the coordination of R.C.A. Guedes) on "Nutrition and Brain Function". The discussions generated during that symposium originated the present text, which analyzes current topics on the theme, based on the multidisciplinary experience of the authors. The way the brain could be non-homogeneously affected by nutritional alterations, as well as questions like early malnutrition and the development of late obesity and hormone abnormalities were discussed. Also, topics like the role of essential fatty acids (EFAs) on brain development, increased seizure susceptibility and changes in different neurotransmitters and in cognitive performance in malnourished animals, as well as differences between overall changes in nutrient intake and excess or deficiency of specific nutrients (e.g. iodine deficiency) were analyzed. It was pointed out that different types of neurons, possibly in distinct brain structures, might be differently affected by nutritional manipulation, including not only lack-but also excess of nutrient intake. Such differences could help in explaining discrepancies between data on humans and in animals and so, could aid in determining the basic mechanisms underlying lesions or changes in brain function and behavior.

Brain↗

Effects of malnutrition during early lactation on development and feeding behavior under the self-selection paradigm.

Selection of food can be affected by several factors, and with the method of self-selection, qualitative changes in nutritional balance may be detected. The goal of the present study was to evaluate feeding preferences in weaning rats using three macronutrients (protein, carbohydrate, and fat), through a free-choice method, evaluating the alteration in their feeding patterns as compared with the previous nutritional status during the early lactation period. We analyzed the effects of protein restriction during lactation over the nitrogen balance after the weaning. The dams were assigned to one of two diet conditions (nourished or malnourished). At weaning, two pups from each litter were housed individually in metabolic cages, and they were maintained on self-selection under a free-choice paradigm and were provided with separate sources of macronutrients. The parameter for evaluating the nutritional effectiveness of the diets was nitrogen balance. We observed that protein intake tended to increase and consumption of carbohydrate and fat tended to decrease progressively during the 3 wk of experiment. In selecting their own food, growing rats and malnourished rats consumed a larger amount of protein than the other rats. Nourished rats selecting their diet had a larger nitrogen balance than nourished rats receiving a composed diet; no nitrogen balance difference was found between the self-selecting groups. Rats can choose an adaptive form when recovering from protein malnutrition.

Animals↗

Ethological analysis of mother-pup interactions and other behavioral reactions in rats: effects of malnutrition and tactile stimulation of the pups.

Mother-pup interaction, as well as other behavioral reactions were studied during the lactation period in 24 litters of Wistar rats and their dams fed either a 16% (control - C; 12 litters) or a 6% (malnourished - M; 12 litters) protein diet. The diets were isocaloric. Throughout lactation there was a 36.4% weight loss of M dams and a 63% body weight deficit in the M pups when compared to control pups. During this period, half of the litters were exposed daily to additional tactile stimulation (CS or MS), while the other half were submitted to normal rearing conditions (CN or MN). The tactile stimulation of pups (handling) consisted of holding the animal in one hand and gently touching the dorsal part of the animal's body with the fingers for 3 min. A special camera and a time-lapse video were used to record litter behavior in their home cages. Starting at 6 p.m. and ending at 6 a.m., on days 3, 6, 12, 15, 18 and 21 of lactation, photos were taken at 4-s intervals. An increase in the frequency (154.88 +/- 16.19) and duration (455.86 +/- 18.05 min) of suckling was observed throughout the lactation period in all groups compared to birth day (frequency 24.88 +/- 2.37 and duration 376.76 +/- 21.01 min), but the frequency was higher in the C (84.96 +/- 8.52) than in the M group (43.13 +/- 4.37); however, the M group (470.2 +/- 11.87 min) spent more time suckling as compared with the C group (393.67 +/- 13.09 min). The M dams showed a decreased frequency of resting position throughout the lactation period (6.5 +/- 2.48) compared to birth day (25.42 +/- 7.74). Pups from the C group were more frequently observed separated (73.02 +/- 4.38) and interacting (258.99 +/- 20.61) more with their mothers than the M pups (separated 66.94 +/- 5.5 and interacting 165.72 +/- 12.05). Tactile stimulation did not interact with diet condition, showing that the kind of stimulation used in the present study did not lead to recovery from the changes induced by protein malnutrition. The changes in mother-pup interaction produced by protein malnutrition of both may represent retardation in neuromotor development and a higher dependence of the pups on their mothers. These changes may represent an important means of energy saving and heat maintenance in malnourished pups.

Analysis of Variance↗

Prenatally malnourished female but not male rats show increased sensitivity to MK-801 in a differential reinforcement of low rates task.

A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and cholinergic systems has previously been identified in predominantly male malnourished animals. The present study sought to compare the effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on responding maintained by a differential reinforcement of low rates (DRL-18s) operant schedule in two groups of rats with different prenatal nutritional histories (well-nourished and protein restricted). The schedule required that the rats space their responses at least 18 s apart in order to obtain food reinforcement (timing behavior). After training to a stable high proficiency, MK-801 was administered to female rats (Experiment 1) at doses of 0 (saline), 0.004, 0.008, 0.016, 0.024 or 0.032 mg/kg (doses expressed as the free-base). MK-801 produced dose-dependent decreases in the percentage efficiency of responding and the number of rewarded responses, with dose-dependent increases in the number of responses emitted. Prenatal malnutrition significantly shifted the inter-response time (IRT) curve to the left, relative to that of the well-nourished controls, leading to a significantly lower efficiency and a lower number of reinforcers, at an MK-801 dose of 0.016 mg/kg. In Experiment 2, the effect of MK-801 on DRL performance was compared between male and female rats after prenatal malnutrition. In general, females proved more sensitive to MK-801 than males. Consistent with Experiment 1, a significantly greater drug impairment was observed in prenatally malnourished females compared with well-nourished females, albeit at a slightly higher dose (0.032 mg/kg). Prenatal malnutrition did not alter the drug response in male rats. These findings suggest that the behavioral response to NMDA blockade is augmented in adult female, but not male, rats after prenatal malnutrition.

Animals↗

Response threshold to aversive stimuli in stimulated early protein-malnourished rats.

Two animal models of pain were used to study the effects of short-term protein malnutrition and environmental stimulation on the response threshold to aversive stimuli. Eighty male Wistar rats were used. Half of the pups were submitted to malnutrition by feeding their mothers a 6% protein diet from 0 to 21 days of age while the mothers of the other half (controls) were well nourished, receiving 16% protein. From 22 to 70 days all rats were fed commercial lab chow. Half of the animals in the malnourished and control groups were maintained under stimulating conditions, including a 3-min daily handling from 0 to 70 days and an enriched living cage after weaning. The other half was reared in a standard living cage. At 70 days, independent groups of rats were exposed to the shock threshold or to the tail-flick test. The results showed lower body and brain weights in malnourished rats when compared with controls at weaning and testing. In the shock threshold test the malnourished animals were more sensitive to electric shock and environmental stimulation increased the shock threshold. No differences due to diet or environmental stimulation were found in the tail-flick procedure. These results demonstrate that protein malnutrition imposed only during the lactation period is efficient in inducing hyperreactivity to electric shock and that environmental stimulation attenuates the differences in shock threshold produced by protein malnutrition.

Animals↗

Prenatal protein malnutrition affects avoidance but not escape behavior in the elevated T-maze test.

An elevated T-maze was used to study the effects of prenatal protein deficiency on inhibitory avoidance and escape behaviors. Female rats were provided with a 25% (control) or a 6% (low protein) casein diets before and during pregnancy. After birth, eight pups in each litter (six males and two females) were fostered to a lactating well-nourished mother. After weaning (21 days of age) all animals received a lab chow diet. Behavioral testing of these offspring began at 70 days of age. To assess inhibitory avoidance, prenatally malnourished and control rats were placed individually at the end of an enclosed arm in an elevated T-maze (one enclosed and two open arms) and the time taken to emerge from this arm was recorded. The same procedure was repeated in 2 subsequent trials given at 30-s intervals. Thirty seconds after the last of these trials, the rat was placed at the end of one open arm and the time taken to withdraw from this arm was measured, thus estimating escape latency. To assess retention, inhibitory avoidance and escape were measured again 72 h later. Prenatally malnourished males and females did not significantly increase avoidance latency from trials 1-3, in contrast to male and female controls. Only control female rats significantly reduced their avoidance latency on the retention test. No significant differences in escape latency were found between diet groups. These results suggest that prenatal malnutrition results in a reduction of anxiety, and that there are gender-specific responses to this test.

Amygdala↗

Prenatal protein malnutrition affects the social interactions of juvenile rats.

The effects of prenatal protein malnutrition on juvenile social behavior was investigated in male and female rats. Animals were provided with 25% (control) or 6% (low protein) casein diets before and during pregnancy. After birth eight pups in each litter (six males and two females) were fostered to lactating control mothers. After weaning (21 days of age) all animals received a lab chow diet until behavioral testing began at 45 days of age. To assess social interaction, pairs of rats of the same gender, consisting of one malnourished and one control rat, were placed in a familiar rectangular arena on 3 consecutive days. Playful social behavior (pin), nonplayful social behaviors (anogenital sniff, walk-over, side-mount, and allogroom), and nonsocial behavior (rear) were recorded in 10-min sessions. Prenatal malnutrition significantly decreased both playful and nonplayful social behaviors, and increased nonsocial rearing. No significant gender differences were observed. The finding that early social behavior is altered by prenatal malnutrition opens the possibility that such changes may play an important role in determining some of the later behavioral differences described in the adult animal.

Agonistic Behavior↗

Malnutrition and reactivity to drugs acting in the central nervous system.

There is a well-established body of data demonstrating that protein or protein-calorie malnutrition experienced early in life is associated with neuroanatomical, neurochemical, as well as behavioral alterations in both animals and humans. A number of studies has focused on the following question: are the neuroanatomical and/or neurochemical changes produced by early malnutrition responsible for the altered behaviors reported in malnourished animals? A tool that has been used to help answer this question is the administration of drugs with specific actions in the various neurotransmitter systems in the central nervous system (CNS). This neuropharmacological approach has produced a considerable amount of data demonstrating that malnourished animals react to drugs differently from controls, suggesting that the altered behavioral expression of these animals could be partly explained by the alterations in the brain function following malnutrition. The present review will provide an overview of the literature investigating the reactivity of malnourished animals to psychoactive drugs acting through GABAergic, catecholaminergic, serotonergic, opioid and cholinergic neurotransmitter systems. Altered responsiveness to psychoactive drugs in malnourished animals may be especially relevant to understanding the consequences of malnutrition in human populations.

Acetylcholine↗

Prenatal protein malnutrition affects exploratory behavior of female rats in the elevated plus-maze test.

To study the effects of prenatal protein deficiency in the exploration of the elevated plus-maze, an ethological procedure was used. Female rats were provided with 25% (control) or with 6% (low-protein) casein diets before and during pregnancy. After birth eight pups in each litter (six males and two females) were fostered to a control mother. After weaning (21 days of age) all animals received a lab chow diet until behavioral testing began at 70 days of age. Individual prenatally malnourished (n = 12) and well-nourished (n = 12) females were placed at the center of the elevated plus-maze and allowed to explore for a 5-min session. One session was given per day for 6 consecutive days. The following variables were recorded: percentage of open arm entries; percentage of time spent in open arms; total arm entries; time in the center platform; latency to first open arm entry; number of attempts to enter an open arm; number of rearings; number of head-dips. The results showed a significant effect of malnutrition on six behaviors (percent open arm entries, percent time spent in open arms, attempts to enter open arms, rearings, head-dips, and latency to first open arm entry) and a significant diet by session interaction on two behaviors (attempts to enter open arms and head-dips). These results indicate increased exploration of the open arms in prenatally malnourished as compared with well-nourished control rats, suggestive of lower anxiety and/or a higher impulsiveness in these animals.

Animals↗

Effects of early protein malnutrition and environmental stimulation upon the reactivity to diazepam in two animal models of anxiety.

In order to investigate the effects of early protein malnutrition and environmental stimulation upon the response to the anxiolytic properties of diazepam, two animal models of anxiety (elevated plus-maze and light-dark transition tests) were used. Rats were malnourished by feeding their dams a 6% protein diet during the lactation period (0-21 days of age) while well-nourished controls received a 16% protein diet. From 21 to 70 days of age all rats received a balanced lab chow diet. Environmental stimulation consisted of 3-min daily handling from birth to 70 days of age. Additional stimulation was provided from 21 to 70 days of age by rearing the rats in an enriched living cage. Eight groups of rats were studied in a 2 (malnourished or well-nourished) x 2 (stimulated or nonstimulated) x 2 (diazepam or vehicle) design. At 70 days of age, independent groups of rats treated with diazepam (2.5 mg/kg, IP) or vehicle were submitted to testing in the elevated plus-maze or light-dark transition procedures. The results showed that both diazepam and environmental stimulation reduced anxiety in the elevated plus-maze; stimulation changed the anxiolytic response to diazepam and the two diet conditions altered differentially the response to both pharmacological and stimulation procedures. These results suggest that environmental stimulation can affect differentially the behavioral response of malnourished and well-nourished rats treated with diazepam.

Animals↗

Acquisition and extinction of jumping, two-way shuttle-box and bar press avoidance responses in malnourished rats: effects of shock intensity.

1. In order to investigate the role of avoidance response and shock intensity in avoidance learning in malnourished rats, three avoidance responses (jumping, two-way shuttle-box and bar press) and three shock intensities (0.4, 0.6 and 1.0 mA) were used. Independent groups of 6 rats were used for each response topography and shock intensity. 2. Malnourished male Wistar rats were suckled by mothers fed a 12% casein diet during the lactation period (0-21 days of age) while the mothers of well-nourished controls received a 25% casein diet. After weaning (21st day), all animals received a commercial lab chow diet until 70 days of age, when the avoidance training started. 3. Malnutrition did not affect the acquisition of the avoidance response, but malnourished groups required more trials to extinguish jumping and two-way shuttle-box. During the acquisition phase all animals learned the jump response faster in comparison to bar press and shuttle-box avoidance responses. Both groups in the acquisition phase responded faster with 1.0 mA when compared to lower intensities (0.6 and 0.4 mA). The malnourished animals showed lower latency of avoidance in the jumping response when compared with well-nourished animals. During the extinction phase there was a significant effect of diet, response topography and shock intensity in the latency to respond and trials to criterion. The increased resistance to extinction in malnourished rats was particularly evident with 1.0 mA in the two-way shuttle-box response. 4. These results suggest that contradictory data related to the acquisition of the avoidance response in malnourished animals cannot be attributed to response topography or variations in shock intensity. Furthermore, our results also indicate that resistance to extinction and latency to respond are appropriate parameters for detecting differences between well-nourished and malnourished animals.

Animals↗

Effects of early protein malnutrition and repeated testing upon locomotor and exploratory behaviors in the elevated plus-maze.

An elevated plus-maze was used to investigate the effects of repeated testing on the locomotor and exploratory behaviors of malnourished rats. Pup malnutrition was induced during the lactation period (0 to 21 days of age) by feeding the dams a protein-deficient diet (6% protein) and the animals were allowed to recover from weaning to 70 days of age by eating a commercial lab chow diet. Control animals were suckled by dams receiving a normal protein diet (16% protein) during the lactation period and were fed a commercial lab chow diet after weaning. At 70 days, malnourished and control animals were placed on the central platform of the elevated plus-maze facing an enclosed arm and allowed to explore for 5 min. This procedure was repeated at 24-h intervals for 6 days. The repeated testing in the elevated plus-maze did not change the total number of arm entries and attempts to enter open arms, but decreased the percentage of open arm entries, time spent in open arms, and total time spent on the central platform. These data suggest an increase in anxiety with repeated testing in the elevated plus-maze. In addition, the malnourished animals showed a larger number of both rearings and attempts to enter the open arms, suggesting a high level of exploration and/or high impulsiveness of these animals as compared to control. The elevated plus-maze proved to be a useful animal model to evaluate exploratory behaviors in early protein malnourished animals.

Animals↗

Comparison of the effects of lab chow and casein diets based on body and brain development of rats.

1. In order to study the effects of protein quantity and quality on development, Wistar rats were submitted to four different diets during lactation and post-lactation periods. Three isocaloric diets were utilized with 6% (M), 16% (W16) and 20% (W20) of protein (casein), and the fourth diet (C) consisted of a commercial lab chow containing 22% protein. 2. During the lactation and post-lactation periods the body weights of dams and pups were recorded weekly. On the 49th day of age (21 days of suckling and 28 days of ad libitum chow), all animals were sacrificed and the brains removed and weighed. 3. Dams from all groups increased food intake during the lactation period, but dams of the M group consumed a lower amount of diet as compared with other groups. Only the body weight of M dams was affected by diet during the lactation period, but the body weight of pups from the M and C groups was lower than in the other two groups. At 49 days of age C and M pups showed a significantly lower brain weight compared with W16 and W20 pups. 4. Thus, a commercial lab chow diet does not promote normal body and brain development as compared with balanced diets containing 16 or 20% protein. These results emphasize the need for further studies in order to evaluate other biological and behavioral parameters that might be altered by a lab chow diet.

Analysis of Variance↗

Effects of early postnatal malnutrition and chlordiazepoxide on experimental aversive situations.

In order to study the lasting consequences of brain changes caused by early malnutrition, rats were fed a protein-deficient diet from birth until 49 days of age and a balanced diet from day 50 to day 70. At 49 and 70 days of age, independent groups of animals were tested in the locomotor activity, step-down inhibitory avoidance, and flinch-jump nociceptive tests. Also, at 49 days of age, malnourished and control rats were sacrificed in order to evaluate the weight of brain regions. Malnourished rats had lower body and brain weights (telencephalon and brain stem) than control rats. Malnourished rats also showed less locomotor activity at the beginning of the test session, lower flinch and jump thresholds, and longer step-down latencies than control animals. Chlordiazepoxide (5 mg/kg, IP) shortened step-down latency of well-nourished rats, but was ineffective in malnourished rats. These and previously reported results indicate that early protein malnutrition causes long-lasting impairment of neuronal systems underlying emotional behavior.

Animals↗

Early life protein malnutrition changes exploration of the elevated plus-maze and reactivity to anxiolytics.

In order to investigate whether protein malnutrition in early life causes lasting changes in reactivity to anxiolytic drugs, exploration of the elevated plus-maze was used. Rat dams during lactation (21 days) and pups after weaning until day 49 of life were fed on 8% casein diet (M rats), while their well-nourished controls received 25% casein (W rats). From day 50 on all animals ate the same balanced diet. Experiments started on day 70. Under the non-drug condition, M rats tended to explore the open arms of the maze relatively more than W rats. Diazepam (0.5-5 mg/kg, IP) dose-dependently increased the percentage of open/total arm entries without significantly affecting the total number of arm entries in W rats. This selective anxiolytic effect of diazepam was considerably smaller in M rats. Ipsapirone (0.5-5 mg/kg) caused a similar though less pronounced anxiolytic effect in W rats, whereas the drug decreased both the % open/total and total arm entries in M rats. In contrast, ritanserin (0.05-1 mg/kg) significantly increased the % open/total arm entries in M rats only, though not in a dose-dependent way. Isamoltane (2.5-20 mg/kg) was ineffective on both M and W rats. These results indicate that early protein malnutrition causes long-lasting alterations in brain systems regulating emotional behaviour.

Animals↗

Decreased reactivity to anxiolytics caused by early protein malnutrition in rats.

In order to investigate whether early malnutrition causes lasting changes in the reactivity to anxiolytic drugs, rat dams during lactation (21 days) and pups after weaning until the 49th day of life were fed on 8% casein diet (M rats), while their well-nourished controls received 25% casein (W rats). From day 50 on all animals ate the same balanced diet. Experiments started on the 91st day. Rats deprived for 22 hours drank water containing either 1.8% or 2.7% sodium chloride for 30 min in a test chamber, total intake being measured. Dose-effect curves for diazepam (0.5-5.0 mg/kg, IP), as well as for the nonbenzodiazepine anxiolytics ipsapirone (0.5-5.0 mg/kg), ritanserin (0.05-1.0 mg/kg) and isamoltane (2.5-20.0 mg/kg) were determined in M as well as in W rats. Diazepam and ipsapirone dose-dependently released drinking suppressed by either salt concentration in W rats, but caused little or no effect in M rats. Ritanserin and isamoltane were ineffective in both groups. These and previously reported results show that early protein malnutrition markedly reduces anticonflict effects of anxiolytics, indicating long-lasting impairment of neuronal systems underlying emotional behavior.

Animals↗