Preweanling Rats Research Articles

Ontogenesis of learning: IV. Dissociation of memory and perceptual-altering processes mediating taste neophobia in the rat.

The rat's neophobic response to tastes can be conceptualized as depending on two processes: memory processes that store a representation of an experienced taste so that it can be recognized as familiar on subsequent encounters, and perceptual-altering processes that respond differentially to novel versus familiar tastes. We investigated the ontogeny of these processes by studying the preweanling rat's behavioral reaction to a 10% sucrose solution. Experiments I and II suggest that the memory processes mature earlier (by 7-8 days of age) than the perceptual-altering processes (about 11 days of age). Experiment III suggests that pups do not acquire an aversion to sucrose paired with illness until they are 12-days-old, implying a close correspondence between the maturation of processes mediating neophobia and taste aversion learning. These findings are consistent with our previous work (Vogt & Rudy, 1984), and our view that ontogenetic dissociations in taste-guided behavior reflect caudal-to-rostral maturation in the ascending gustatory system.

A specialization of taste aversion learning during suckling and its weaning-associated transformation.

During ontogenesis, altricial mammals advance through different ecological niches which require correspondingly different adaptive strategies. We view learning as an important feature of ontogenetic adaptations and consider the acquisition and expression of taste aversion learning during nursing within this framework. Fifteen-day-old preweanling rat pups fail to acquire conditioned taste aversions while nursing, whereas 20-day-old weanlings readily learn flavor aversions while suckling (Martin & Alberts, 1979). The developmental emergence of taste aversion learning while nursing coincides with reduction in maternal milk supply and the rat pup's transition to a solid food diet. We considered the ontogenetic transformation of learning while nursing as a feeding-related adaptive strategy of the weanling rat and tested two predictions derived from this view: (1) delayed weaning might postpone acquisition or expression of suckling-related taste aversions and (2) conditions that permit weaning (e.g., access to alternate food sources) might induce acquisition or expression of such taste aversions. Both predictions were confirmed.

The maternal pheromone and deoxycholic acid in relation to brain myelin in the preweanling rat

We examined the lipid composition of blood and myelin in preweanling rats denied access to maternal feces. Levels of triglycerides and free fatty acids in the blood were reduced and in the brain the amount of myelin and the phospholipid concentration in myelin were also reduced. The addition of deoxycholic acid to ordinary laboratory chow prevented these deficiencies. We conclude that response to the maternal pheromone and the subsequent ingestion of deoxycholic acid through maternal feces promotes the deposition of normal brain myelin.

The maternal pheromone and brain development in the preweanling rat

Preweanling rats selectively approach and consume pheromone-containing maternal feces. This selectivity suggests that the consumption of maternal feces might be important for the growing pup. Previous research suggested that such feces might promote brain development. A series of experiments was carried out in which pups were denied access to maternal feces. These pups were clearly inferior to control pups in brain growth and neurobehavioral maturation, as well as in the quantity of brain myelin.

The maternal pheromone, not maternal odors, as an innate stimulus for the preweanling rat: a reply to Rosenblatt.

The maternal pheromone, not maternal odors, as an innate stimulus for the preweanling rat: a reply to Rosenblatt.

THE EFFECT OF IMMATURITY ON INTESTINAL HANDLING OF COW'S MILK PROTEINS

To investigate postnatal maturational changes of gut barrier function, we used two small intestinal in vitro models. Microvillus membrane (MVM) preparations were used for studying membrane surface binding and the everted gut sac technique was used for studying mucous coat binding and uptake of 125I-labelled bovine serum albumin (125I-BSA) and betalactoglobulin (125I-BLG) in newborn, preweanling and adult rats. Surface binding of BSA and BLG to MVM was greater from newborn and preweanling rats, compared to adults (BSA, newborns: 2.74±0.53%; adults 1.08±0.17%, p<0.001). Binding however was weak and nonspecific. Contrary to surface binding, mucous coat binding of BSA and BLG to preweanling gut sacs was less than to adult ones, as was uptake (BSA binding: 0.94±0.30 vs 3.06±0.74 μg 125I-protein equivalents /mg mucosal protein, p<0.001; BSA uptake: 0.35±0.17 vs 0.71±0.20, p<0.01). Gut sac binding and uptake were closely correlated in adult and preweanling animals (r=0.76, p<0.001 for BSA; r=0.85, p<0.001 for BLG in preweanlings). These studies suggest that immature animals are binding more cow's milk proteins to their MVM, but that less protein is bound to the mucous coat and taken up by immature gut sacs. Differential handling, mucous coat and MVM binding of food proteins in immature animals may be controlled by mucus layer factors which act to protect the underlying MVM.

Cholinergic mediation of spatial memory in the preweanling rat: Application of the radial arm maze paradigm.

These experiments assessed spatial memory capabilities in the developing rat by the radial arm maze paradigm. Subjects were trained and tested in the maze beginning at 16 days until they were 25 days of age. Results showed that animals that received training performed significantly better than those naive to the task, and better than chance, which suggests an early capacity for this type of learning. The second experiment investigated the neural mechanism that underlies spatial memory at this age as measured by the radial arm maze. In order to distinguish between the working and the reference memory components of the task, a modification of the basic radial arm maze paradigm was used. Subjects trained from 16 days received drug injections of saline, methylscopolamine, scopolamine, or arecoline prior to testing at age 25 days. Results indicated that central cholinergic antagonism severely impairs working memory while sparing reference memory. This finding is consistent with the existing literature that suggests a role for acetylcholine in adult learning and memory, specifically in working memory. Most important, these experiments document that (a) the radial arm maze paradigm can be used effectively for the developmental study of learning and memory in the rat and (b) cholinergic system(s) mediate working memory at an early age.

Cholinergic mediation of spatial memory in the preweanling rat: Application of the radial arm maze paradigm.

Cholinergic mediation of spatial memory in the preweanling rat: Application of the radial arm maze paradigm.

Self-stimulation in 7- and 10-day-old rats.

Recently, it has been shown that the infant rat exhibits learned behaviors characteristic of the adult. With a modified self-stimulation paradigm, this study explored whether 7- and 10-day-old rat pups could learn a discriminated operant to obtain direct electrical stimulation in neural sites that support self-stimulation in adults. By nudging one of two response manipulanda, at two ages (7 and 10 days) and temperatures (22 and 35 degrees C), pups self-stimulated with electrodes implanted in a variety of forebrain sites, including the prefrontal cortex, bed nucleus of the stria terminalis, medial nucleus of the amygdala, and the medial forebrain bundle. The only temperature-sensitive site might be the nucleus accumbens which was positive only at the higher temperature in 10-day-olds. These results indicate that several forebrain sites demonstrate rewarding properties of stimulation in the preweanling rat pup.

Somatic and central nervous system growth in artificially reared rat pups

Rearing preweanling rat pups away from their mothers by feeding through chronic intragastric cannulas has been shown to result in alterations in the growth of specific organs. In the present study, artificially reared (AR) rats and their normally reared (NR) siblings were sacrificed at various ages during this procedure to determine the time course of these alterations. Brain growth deficits were detected within 24 hours, peaked after 8 days of artificial rearing and showed some recovery by the end of the study. By day 18, the livers, kidneys and spleens of the AR pups were significantly larger than those of their NR siblings. The spleens showed an initial decrease in weight compared to the spleens of the NR pups. However, by day 18, the spleens of the AR group were significantly larger than those of the NR group.

The influence of environmental variables on amphetamine-induced activity in the preweanling rat

The present experiments investigated how environmental stimuli influence a behavioral response to amphetamine treatment in preweanling rats. In the first experiment, 15-day-old rats received either 1 mg/kg d-ampethamine or saline and were observed in the presence of their home shavings or in a novel cage. Results showed that although familiar cues from the home bedding decreased activity of the saline treated pups, these cues did not influence the activity-enhancing effect of amphetamine. In Experiment 2, 15-day-old pups were placed in a cage with an anesthetized adult conspecific and non-directed activity, around the cage, as well as directed activity on top of the adult were recorded. Following amphetamine treatment, animals tested with a conspecific showed no increase in non-directed activity, a finding which replicates previous observations. In the present experiment, however, a significant increase was seen in the activity directed towards or on top of the anesthetized adult. These experiments reveal that familiar cues per se are not sufficient to influence amphetamine-induced activity in young rats. Activity is influenced, specifically if familiar cues are associated with a discrete object. In the presence of a familiar stimulus, non-directed activity is decreased and directed activity is enhanced. These data are discussed in terms of clinical findings which slow that amphetamine acts to focus, or direct activity of the hyperactive child, and further underlines the importance of environmental variables in influencing the amphetamine response.

Ontogeny of stress effects on ornithine decarboxylase activity in rats

This study demonstrates that “stress” elicits a specific pattern of organ response in developing rats that is determined by the particular “stress” and by the age of the animal. Maternal deprivation (MD) of preweanling rat pups decrease ornithine decarboxylase (ODC) activity in many tissues, as reported previously, while immobilization (IMM) and cold stress increase ODC activity in liver and heart of neonatal rat. Serum GH is decreased by MD and by IMM, but is not affected by cold stress. Stress-induced ODC elevation increases with age, while MD effects disappear at weaning. IMM and cold increase ODC activity in kidney, liver and heart of adult rats. These effects of IMM are blocked by the ganglionic antagonist chlorisondamine in adult but not in neonatal rats. The results of this study suggest that MD and the “classical” stress paradigms IMM and cold evoke different patterns of organ ODC response in neonatal rats. Furthermore, these findings suggest that the mechanism by which immobilization increases ODC activity changes from a hormonal to a neural mechanis, during ontogeny.

Preferences of pre-weanling Long-Evans rats for anal excreta of adult males and females

Long-Evans hooded rat pups were reared with their dam alone, their dam and sire or their dam 12 hrs per day and their sire 12 hrs per day and tested for preferences for anal excreta from adult male and female rats when they were 18 to 20 days of age. In all rearing conditions the anal excreta of the rat's own dam was preferred to that of strange dams and the excreta of both own and strange dams was preferred to that of virgin females. Anal excreta from virgin females was preferred to no odor as was anal excreta of unmated males, strange sires and the rat's own sire. Only rats reared with their dam and sire preferred the odor of their own sire to that of other males. The results suggest that pre-weanling rats may attend to different dimensions of the odors of conspecifics, such as the species odor, maternal odor, and individual odor and that different rearing conditions may influence the odor dimension to which the rat attends.

Appetitive instrumental training in preweanling rats: I. Motivational determinants.

Two experiments tested learning and retention of preweanling rats (10, 15, and 23 days of age) with an appetitive T-maze spatial discrimination task, using 3 different reinforcers for training (Mother Alone, Mother + Milk, and Milk Alone). The hypothesis was that immature rats are prepared to select and generate effective hypotheses for learning in an environment bearing some similarity to the home nest prior to their exhibiting similar capacities in other contexts. In Experiment I, we found support for this hypothesis in that 10- and 15-day-old rats were able to acquire the maze task when reinforced with Mother Alone or Mother + Milk, but not when reinforced with Milk Alone. In Experiment II, we report that 23-day-old rats weaned at 19 days postpartum were better at learning the maze task with milk as the reinforcer than littermates raised until training with the dam. We hypothesize that the development of foraging strategies might be necessary for the expression of maze behaviors reinforced with milk alone.

Effect of age on benzodiazepine-induced behavioural convulsions in rats.

The benzodiazepines are a class of drugs used to alleviate anxiety. As such they constitute one of the most commonly prescribed compounds, due in part to their efficacy and safety. The physiological effect of these drugs is probably through interactions with a low affinity benzodiazepine binding site and two (types 1 and 2) higher affinity sites. The ontogenesis of these latter two binding sites in the rat differs, with the type 2 binding site being predominant at birth and the type 1 binding site increasing in number after the second week after birth. The differential development of these two receptor types is important because the immature organism may have different physiological and behavioural responses from the adult. Here we demonstrate an important difference: that a prototypic benzodiazepine, chlordiazepoxide, and a water-soluble benzodiazepine, flurazepam, produce behavioural convulsions in the preweanling rat. The convulsions are antagonized by the benzodiazepine blocker Ro-15-1788. The triazolopyridizine CL-218872, specific to the type 1 receptor, does not share this action. We suggest that this paradoxical convulsant effect of chlordiazepoxide and flurazepam is due to activation of the type 2 receptor in the absence of the type 1 receptor in the immature rat.

Age-related differences in the preweanling rat’s reactivity to footshock

Unconditioned reactivity to footshock in 5-, 7-, 9-, 11-, and 13-day-old rats was assessed by measuring locomotor activity elicited by inescapable shock. Five-day-old rats differed in activity from all ages except the 7-day-olds. The 7-day-olds were less active than the 13-day-olds, and the 9-13-day-olds failed to differ from one another. These findings suggest that an age difference in reactivity to footshock was probably not a determining factor in reported age-related differences in the shock-escape behavior of infant rats.

Effect of short-term ischemic trauma on the hepatic cytochrome P-450 monooxygenase system in the neonatal rat.

Abdominal aorta ligation in neonatal rats was used as a model to evaluate drug-metabolizing activities after trauma. Short-term ischemic trauma (24 h) was found to have a significant effect on hepatic microsomal cytochrome P-450 content, NADPH-cytochrome c reductase activity, and cytochrome P-450-dependent electron transport capacity. In pre-weanling animals, trauma caused a decrease in hepatic microsomal cytochrome P-450 content, but increased NADPH-cytochrome c reductase activity. The electron transport capacity of the cytochrome P-450 system is reduced in traumatized pre-weanling rats, suggesting that cytochrome P-450 may be the rate-limiting step for this enzyme system in animals of this age. After weaning, the electron transport capacity of this enzyme system is greater in traumatized animals than in control animals, indicating that a different rate-limiting factor dominates in these animals.

Toxic effects of maternal methadone administration on cardiac development in the neonatal rat: Potential participation of altered polyamine levels in growth impairment

The pattern of development of polyamine levels in hearts of preweanling rats whose mothers received methadone indicated initial deficits in both spermidine and spermine followed by rebound elevations, a pattern consistent with delayed cellular development. Since polyamines are thought to play important roles in nucleic acid and protein synthesis during cellular maturation, these alterations may participate in the retardation of tissue growth seen in the perinatal opiate syndrome.

Preferences of pre- and post-weanling long-evans rats for nest odors

Three experiments were conducted on the preferences of infant rats for nest odors. Pre-weanling rats preferred their own nest odor to nests of strange litters and showed low preferences for the nest odors of virgin females. Nest odors of unmated males were investigated less than the pup's own nest odor but more than the odors of virgin females. Male and female rats did not differ in odor preferences. Rats reared with both their dam and sire did not differ in their odor preferences from rats reared with their dam alone when tested at 16–20 days of age, but when tested at 33–38 days of age they showed a greater preference for male odors. Post-weanling rats did not show a preference for the nest odors of lactating females and began to show sex differences in their preferences.

The effects of opiate antagonists on milk intake of preweanling rats

The observation that acute administration of opiate agonists to rodent adults increased food intake while the reverse was true with a single injection of an opiate antagonist has led to the suggestion that endogenous opioids may in part mediate feeding behaviour in adult rodents. Studies were performed in infant rats to explore further the generality and ontogeny of this function. In three models of food availability, the effects of naloxone and naltrexone were assessed in deprivation-induced feeding tests in 3-, 10-, 12-, 14- and 19-day-old preweanling rats. Naloxone or naltrexone attenuated food intake only after 14 days. Functional immaturity of the opioid systems vis-a-vis ingestive behaviour may account for this developmental sequence.