Development of stress-induced responses in preweanling rats.

This study examined in postnatal Days 7, 14, and 21 male rats the effects of social isolation and social isolation with administration of brief foot shocks on the development of stress-induced behavioral and pituitary-adrenal hormone responses. Day 21 rats appeared similar to adult rats in their repsonses to the two test conditions. That is, exposure to either isolation or to shock increased both pituitary-adrenal hormone secretion and tail-flick latencies but only administration of shock potentiated freezing and ultrasonic vocalizations. Younger rats differed from Day 21 rats in their responses to the two test conditions. In both tests, Day 7 rats produced the highest number of ultrasounds, which may be due to a significant decrease in body temperature. In contrast, in Day 14 pups, exposure to shock significantly reduced isolation-induced ultrasonic vocalizations. Additional age-dependent differences were found in the analgesic responses of Days 7 and 14 rats. Day 7 rats exposed to stress became consistently hyperalgesic whereas Day 14 rats showed only a short-lasting analgesic response. Although in Days 7 and 14 rats exposure to the two stress conditions produced significant elevations in pituitary-adrenal hormone concentrations, plasma levels were lower than those measured in Day 21 rats. To summarize, preweanling rats exhibit varied age-dependent responses when exposed to different stress environments.     

Alleviation of forgetting in preweanling rats

Three experiments tested the learning and retention of neonatal rats (7, 9, and 12 days of age) with a nondirectional active avoidance task, using a vibrotactile conditioned stimulus. The hypothesis was that the substantial deficit of these animals in 24-hr retention is due, at least in part, to a deficiency in memory retrieval. In Experiment I, a reactivation treatment was found to alleviate the forgetting over the 24-hr period for 12-day olds although having somewhat lesser effect for animals 9 days of age. The reactivation treatment seemed ineffective for rats 7 days of age. Experiments II and III confirmed the reliability of the reactivation effects with 9- and 12-day olds, while adding further control conditions and providing new information concerning the ontogenesis of latent inhibition.     

Maternal regulation of the adrenocortical response in preweanling rats.

In the following studies, we investigated the effects of 24-h maternal deprivation on the infant's hypothalamic-pituitary-adrenal system. Experiment 1 examined the effect of deprivation on the infant's corticosterone (CORT) response to adrenocorticotropin hormone (ACTH) injection. At all ages studied, deprivation resulted in a potentiation of the response. At some ages, deprived nontreated pups had higher CORT levels than nondeprived pups. Experiment 2 examined the ontogeny of the deprivation-induced stress response, and the capacity of the mother to inhibit it. From 8 days of age onwards, deprived animals showed a CORT response to saline injection that was either absent or far smaller in nondeprived pups. Saline-induced CORT secretion was diminished, or prevented, by returning the infant to its dam. Maternal reunion had no effect on ACTH-induced CORT elevations. Finally, Experiment 3 investigated the effects of deprivation over a more extended period of time. In maternally deprived pups, ACTH-induced CORT elevations persisted for at least 2 h following reunion, but by 6 h had returned to baseline. These data suggest that maternal factors are involved in the regulation of the responsiveness of the pup's hypothalamic-pituitary-adrenal system.     

Appetitive behavior of rats in a T-maze following unilateral hypothalamic lesions.

Reacquisition of position responses in a T-maze are significantly disrupted following unilateral lateral hypothalamic lesions if a response is required contralateral to the side of the lesion. This disruption is more severe in animals trained on a shock motivated task than in those trained on a water acquisition task. Animals trained to turn ipsilateral to the lesioned side on water acquisition showed no such deficits, suggesting disruption of sensory-motor mechanisms rather than specific interference with memory or relearning. Evidence indicates that the differential responding of thirst and shock motivated animals was not due to differences in response strategies.     

Appetitive conditioning in neonatal rats: Conditioned orientation to a novel odor

These experiments document a form of early appetitive learning in rats obtained using classical conditioning procedures. Some of the special determinants of this conditioning are described, as well as ontogenetic changes in the effectiveness of training procedures. Learning was apparent when deprived 3- and 6-day-old rats oriented to and maintained contact with a novel and normally aversive odor after this odor had been paired with oral infusions of milk (Experiment I). The effectiveness of the conditioning procedures depended on the temperature at which pups were trained (Experiment IB). Moreover, the reinforcing properties of milk infusions depended on deprivation (Experiment IC). This conditioned change in responsiveness to odor was specific to the odor that had been paired with milk (Experiment II) and was retained for at least 24 hr (Experiment III).     

Cued platform training reveals early development of directional responding among preweanling rats in the Morris water task

Previous studies on the ontogeny of spatial learning report that rats younger than 19–21 days of age are incapable of learning the location of a platform relative to distal cues in the Morris water task. Here, we manipulated the spatial relationship of a cued platform to the pool and the distal visual room cues to investigate whether distal cues can control navigation among 16‐ to 24‐day‐old rats. Rats were trained to navigate to a cued platform in a rich distal cue environment. During critical test trials, the pool was shifted to a different, overlapping position and the cued platform was placed either in the same absolute location in the room or the same relative location in the pool as during training. Rats aged 17 days and older exhibited a disruption in performance when the cued platform was in the absolute location but not the relative location, indicating that rats had learned the direction of the cued platform within the distal cue environment. These observations indicate that (1) information acquired from distal room cues influences navigation as early as 17 days of age, (2) this distal cue information is preferentially used to guide navigation in a particular direction rather than to a precise place in the room, and (3) the directional nature of the influence of distal cues on navigation is invariant across development. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 53: 1–12, 2011.     

Within-species variation in the development of ultrasonic signaling of preweanling rats.

The development of litter and individual differences in the rate of ultrasonic signaling of neonatal rats was studied. Systematic variations among litters and individuals emerged, without differential treatment. These differences were not correlated with variations in general development as indexed by body weight. Two experiments using a cross-fostering design showed that litter differences developed independently of variations in postnatal environment. These results indicate that the variations among litters in ultrasound rate have a prenatal, possibly genetic, etiology and may represent reliable indicants of response to environmental stress.     

Social learning about ethanol in preweanling rats: role of endogenous opioids

The role of the endogenous opioid system in social learning about ethanol was examined in three experiments using preweanling rats. Experiment 1 showed that interactions with intoxicated siblings in the home cage on postnatal Days (PD) 12, 14, and 16 results in increased voluntary intake of ethanol when subjects are tested 24 hr after the final exposure. The results also suggested that the endogenous opioid system is not involved in acquisition. Administration of naloxone during social exposure to ethanol had no effect on later ethanol intake. Experiment 2 examined the effects of receptor‐selective antagonists administered prior to test. For subjects that had social exposure to ethanol, intake of ethanol was completely suppressed by either naloxone or the δ antagonist naltrindole. For ethanol‐naïve subjects, intake also was completely suppressed by naloxone. However, intake was partially blocked by naltrindole or the μ antagonist β‐FNA. Experiment 3 confirmed the differential involvement of μ and δ receptors in ethanol intake through a more comprehensive dose–response analysis of β‐FNA and naltrindole. Collectively, these data reveal that learning about ethanol from intoxicated conspecifics not only affects voluntary intake of ethanol but also alters the opioidergic response to ethanol consumption. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 132–139, 2004.     

Postnatal naltrindole treatments induce behavioural modifications in preweanling rats

To investigate the physiological role of the delta-opioid receptor during the preweanling period, we have studied the effects of chronic (daily injections from birth to postnatal day 19) and acute treatments with the selective delta-antagonist naltrindole (1 mg/kg), on behavioural and nociceptive responses in 20-day old male rats. Behavioural testing was performed using an open field paradigm. Acute naltrindole induced significant decreases in external and total ambulation (horizontal activity) and rearing behaviour (vertical activity), as well as a significant increase in grooming frequency. In animals chronically treated with naltrindole there was an increase in total ambulation one day after the discontinuation of the treatment. In a test of nociception (tail immersion) no significant effect of chronic naltrindole treatment on baseline latencies or of acute naltrindole on latency quotients (post-treatment latency/pre-treatment latency) were found. However, chronic naltrindole administration significantly decreased the latency quotients. The results show that the delta-opioid receptor participates in the tonic regulation of motor activity during the preweanling period and might be involved in certain aspects of stress responsiveness.     

Maternal contact inhibits pituitary-adrenal stress responses in preweanling rats

Three experiments examined psychological factors which inhibit pituitary-adrenal activity in 12-, 16-, and 20-day-old rats. Infant rats were placed in heated novel test arenas for 30 min--a treatment which increases corticosterone secretion--and were presented with different appetitive stimuli in order to determine whether these stimuli inhibit this increased hormone secretion. The first experiment was a factorial combination of two conditions: suckling an anesthetized dam and milk ingestion through an intraoral cannula. At all ages, suckling inhibited corticosterone secretion but milk ingestion did not, nor was there an interaction of these factors. In the second experiment, the importance of suckling was assessed by allowing pups' contact with an anesthetized dam either with or without the opportunity to suckle. At all ages, contact with suckling and contact alone were equally effective in inhibiting corticosterone secretion. The third experiment asked whether contact with a lactating female is necessary for pituitary-adrenal inhibition or whether more distal cues associated with lactation are sufficient. Pups were tested under one of four treatments formed by a 2(Lactating vs. Virgin Female) X 2(Contact vs. No Contact) factorial design. At all ages inhibition of corticosterone secretion occurred only in animals which were allowed contact with an anesthetized female. Lactating and virgin females were equally effective for the 12- and 16-day-old pups, but contact with a virgin female was less effective for the 20-day-old pups. These findings indicate that neuroendocrine mechanisms subserving inhibition of the pituitary-adrenal system exist during the preweanling period in the rat, and suggest the possibility of maternal regulation of this physiological system during development.     

The ontogenesis of defensive reactions to shock in preweanling rats

Behavioral observations were made on the reaction to tailshock and footshock in 5- to 20-day-old hooded rats. For detection thresholds, age differences were found for footshock but not for tailshock. During intershock intervals, more generalized activity and freezing were elicited by footshock, whereas more responding directed to the shock source was elicited by tailshock. The unconditional responding to shock indicated that the older animals had a larger behavioral repertoire of defensive reactions and responded differentially to different shock intensities. The younger animals appeared to have a more limited and stereotyped repertoire of defensive reactions and to be more sensitive to the same nominal shock level. These normative data should prove useful in evaluating motivational and response repertoire problems when assessing learning processes developmentally.     

Ontogeny of behavioral inhibition induced by unfamiliar adult male conspecifics in preweanling rats.

Previous studies showed that when socially isolated at 22 degrees C, postnatal day 14 rats, but not younger day 7 rats, reduce their emission of ultrasonic vocalizations when exposed to an unfamiliar adult male rat, a naturalistic threat. Because ultrasound production is associated with factors such as age and body temperature, this study examined in age-appropriate thermoneutral temperature ranges whether preweanling rats of different ages are equally capable of inhibiting their emission of ultrasounds when threatened. In Experiment 1, 7- and 14-day-old rats were socially isolated and exposed to unfamiliar anesthetized adult male rats in a thermoneutral environment. Only 14-day-old rats significantly reduced their emission of ultrasounds. This reduction in ultrasound production was accompanied by freezing. In Experiment 2, additional ages were examined under identical test conditions. At 3, 6, and 9 days of age, pups frequently emitted ultrasounds when exposed to the anesthetized male rat. However, at 12 days of age, rat pups responded to the anesthetized male rat by freezing and significantly reducing their emission of ultrasounds. Results indicate clearly that under the present testing conditions the ability of rat pups to inhibit ultrasounds and freeze when threatened is not present at birth but emerges by the end of the second postnatal week.     

Acquisition and retention of multidirectional escape behavior in preweanling rats

The shock-escape behavior of preweanling rats in a multidirectional escape situation was examined in 3 experiments. In Experiment I, 5-, 7-, 9-, and 11-day-old rats were given shock-escape training on each of 3 days. Rats younger than 7 days of age did not improve escape responding within or over sessions. Animals 7 days of age and older, however, showed both an intrasession improvement and an intersession improvement that could not be attributed solely to maturation. In Experiment II, the escape behavior of 3-, 5-, and 7-day-olds was examined in an apparatus modified to take into account the poor locomotor abilities of these animals. They were given escape training on 3 successive days. Again, no within-session improvement was found in rats under 7 days of age. However, an intersession improvement was found in rats whose training began at 5 days of age. This improvement was due to maturation and did not reflect a cumulative effect of training. Experiment III, like Experiment I, demonstrated that the intersession improvement in the older rats was not simply a maturation effect. It also demonstrated that the improvement could not be attributed to the stress of prior handling, shock, or body temperature loss, but was, rather, a retention effect. These results support the contention that the emergence of memory is task specific.     

Artificial rearing of preweanling rats: the effectiveness of direct intragastric feeding

The stimulating effects of amino acids and related compounds on the gustatory receptors were studied in the Japanese minnow, Pseudorasbora parva, by recording electrical responses from the palatine nerve innervating the upper lip and the adjacent palate. All of the 21 amino acids and 6 related compounds elicited responses at a concentration of 10^?3 M. The order of the response magnitude to the 6 most effective of 18 L-amino acids was: proline > lysine-HCl > alanine > arginine-HCl > cysteine > serine. The threshold concentration for proline, the most potent among the amino acids was estimated to range between 10^?11 and 10^?10 M. The relationship between the log response magnitude and the log stimulus concentration for L-proline or L-alanine was linear in a relatively wide concentration range, showing a tendency for the response to be saturated at higher concentrations. The results of this study indicate that the amino acids are the most potent gustatory stimuli in the Japanese minnow among various chemicals so far tested including salts, sugars, quinine-HCl and ribonucleotides.     

The unconditioned stimulus pre‐exposure effect in preweanling rats in taste aversion learning: Role of the training context and injection cues

The unconditioned stimulus pre‐exposure effect (US‐PE) refers to the interference paradigm in which acquisition of the conditioned response is retarded due to prior experience with the US. Most studies analyzing the psychological mechanisms underlying this effect have been conducted with adult rats. The most widely accepted hypothesis explains this effect as a contextual blocking effect. Contextual cues associated with the US block the conditioned stimulus (CS)‐US association during conditioning. The modulatory role of a context devoid of distinctive olfactory attributes is not observable until approximately PD23 in rats, including modulation of interference paradigms such as latent inhibition or extinction. In this study, we analyzed US‐PE in preweanling rats along with the role of the training context in this effect in terms of conditioned taste aversion preparation. Pre‐exposure to LiCl before conditioning retarded the acquisition of taste aversion. The US‐PE was observed in preweanling rats when, during pre‐exposure, subjects were exposed to the conditioning context, and this effect was not attenuated either by the administration of the US in a familiar environment (Experiment 1a), or by the presence of an alternative, more salient context during pre‐exposure (Experiment 1b). Additionally, the US‐PE was still observed when the route by which the US was administered was changed between the pre‐exposure and conditioning phases (Experiment 2a) as well as when the injection cues were removed during conditioning (Experiment 2b). These experiments show a strong US‐PE in preweanling rats and fail to support the contextual blocking hypothesis, at least in this stage of ontogeny. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 193–204, 2013     

Improved instrumental learning in neodecorticate rats

The first experiment describes the improvement in instrumental learned behaviour which can be achieved by pretraining in rats surgically deprived of neocortex. The pretraining consisted of allowing the animal to learn in gradual steps to attend to and manipulate a chain for a food reward which was delivered to a food tray some distance from the chain itself. Following this pretraining the neodecorticates were able to progress to operating the chain up to 60 times for a single reward and distributed their behaviour between the chain and the food tray in the same way as normal animals. Without pretraining neodecorticated rats have previously not shown such high levels of performance and have failed to separate the instrumental response and the reward directed components of their behaviour. In a second experiment the source of conflict between reward oriented behaviours and the instrumental response itself was removed by allowing the animal to make its instrumental responses to the food tray door. Again normal levels of performance were seen in the neodecorticated animal. It is concluded that neocortex is not a prerequisite for efficient instrumental learned performance even when a particular response must be repeated many times for a single reward. The possibility that the neodecorticate initially has difficulty in identifying or paying attention to the object to be manipulated in this type of situation and so, unless appropriately pretrained, fails to separate reward oriented behaviours from the instrumental response, is discussed.     

Kinematic analyses of air-stepping in normal and decerebrate preweanling rats

We studied the ability of L-DOPA (100 mg/kg, subcutaneous) to elicit air-stepping in decerebrate and sham-operated Sprague-Dawley rats from postnatal Day 5 through postnatal Day 20. The most common gait consisted of fore- and hindlimb alternation, but between 10 and 20 days of age, patterns of coordination resembling swimming, in which the forelimbs remained adducted, and galloping became more frequent in both decerebrate and sham-operated rats. Because episodes of galloping were rarely more than two or three step cycles in length, our analyses focused on episodes of stepping in which limbs within the girdles stepped in alternation and diagonal pairs of limbs moved in synchrony ("trot"). The rate of stepping of both decerebrate and sham-operated rats increased from about 2.9 steps/s at Day 5 to about 4 steps/s at Day 20. In both groups, this increase was found to result from a decrease in the duration of the retraction phase of the step cycle. Amplitudes of movement at the wrist, knee, and ankle increased with age in both decerebrate and sham-operated neonates, whereas those of the shoulder, elbow, and hip did not change in either group. The timing of movements at joints within each limb also changed similarly with age in sham-operated and decerebrate pups. During development, forelimb movement was increasingly led by the wrist, which was followed by the elbow and then finally by the shoulder. Hindlimb movements were increasingly led by the knee, followed by the ankle, and finally by the hip. At all ages, diagonal limbs moved in synchrony, and heterolateral limbs within each girdle moved in antiphase. However, the phase relationship between hindlimb and forelimb movements changed both in sham-operated rats and in decerebrate rats during ontogeny. On Day 5, movement of each hindlimb was phase-delayed relative to that of the diagonal forelimb whereas on Days 15 and 20, the hindlimb was phase-advanced. The parallel emergence of different gaits and the similarity of coordination during diagonal progression in sham-operated and decerebrate pups show that age-related changes in gait are mediated no more rostrally than the midbrain.