Complete maternal deprivation affects social, but not spatial, learning in adult rats

The effects of maternal deprivation on learning of social and spatial tasks were investigated in female adult rats. Pups were reared artificially and received "lickinglike" tactile stimulation (AR animals) or were reared with their mothers (MR animals). In adulthood, subjects were tested on paradigms of spatial learning and on paradigms involving learning of social cues. Results showed that maternal deprivation did not affect performance on spatial learning, but it did impair performance on the three social learning tasks. The AR animals made no distinction between a new and a previously presented juvenile conspecific. AR animals also responded less rapidly than MR animals at test for maternal behavior 2 weeks after a postpartum experience with pups. Finally, AR animals did not develop a preference for a food previously eaten by a familiar conspecific whereas MR animals did. This study indicates that animals reared without mother and siblings show no deficits in spatial tasks while showing consistent deficits in learning involving social interactions.     

Cytotoxic lesions of the hippocampus increase social investigation but do not impair social-recognition memory

A number of studies have implicated the hippocampal formation in social-recognition memory in the rat. The present study addressed this issue directly by assessing the effects of cytotoxic lesions confined to the hippocampus proper, encompassing the four CA subfields and the dentate gyrus, on this behavioural task. Ibotenate-induced hippocampal lesions led to locomotor hyperactivity and a marked spatial working-memory impairment on the elevated T-maze. In addition, they also led to increased social investigation. However, despite these clear effects, there was no effect of the lesions on social-recognition memory. These results suggest that the hippocampus proper does not subserve social-recognition memory; but does not, however, preclude the possibility that other areas of the hippocampal formation (e.g. entorhinal cortex or subiculum) may support this memory process.     

Neonatal social isolation alters both maternal and pup behaviors in rats

The development of emotional behavior is dependent on the early experiences of the infant and the quality of maternal care. In these experiments, the effects of social isolation during the preweaning period on both pup behavior and maternal responsivity were examined. In the first study, the number of ultrasonic vocalizations (USVs) emitted after brief maternal separation was measured in neonatal rats with differing histories of social isolation. The social isolation procedure consisted of 5 days of daily separation from the dam and littermates for either 3 or 6 hr. At both ages tested, socially isolated pups vocalized significantly less than control pups. In the second study, the effects of prior isolation either daily for 5 previous days (Chronic Isolation) or for 4 hr prior to testing (Acute Isolation) were examined in a T-maze choice test. Pup vocalizations in the presence of the dam and dams' maternal behavior were assessed. When the dam was confined to the start box or during the maternal free access period, both Chronic and Acute Isolates vocalized less than pups that had never left the home nest. Dams spent more time with and licked and groomed more frequently and for a longer time both Chronic and Acute Isolates compared to pups that had always been with dams in the home nest. These results suggest that early isolation experience can alter subsequent responses to separation stress in neonatal rats and that maternal behavior is sensitive to the prior experiences of offspring.     

Quantitative changes in reduced nicotinamide adenine dinucleotide phosphate-diaphorase-reactive neurons in the brain of Octodon degus after periodic maternal separation and early social isolation

The influence of preweaning maternal separation and postweaning social isolation on the development of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase-reactive neurons in prefrontal cortical areas, in subdivisions of the nucleus accumbens and in the corpus callosum was quantitatively investigated in the precocious rodent Octodon degus. Forty-five-day-old degus from three animal groups were compared: (i) degus that were reared under normal undisturbed social conditions; (ii) degus that were repeatedly separated from their mothers during the first three postnatal weeks and thereafter reared with their family; and (iii) degus that remained undisturbed with the family until weaning (postnatal day 21) and thereafter were reared in social isolation. Preweaning maternal separation led to a significant decrease in NADPH-diaphorase-containing neurons in the corpus callosum in both genders (down to 33%) compared with the social control group. No significant changes were found in the subregions of the medial prefrontal cortex and nucleus accumbens. Postweaning social isolation led to a reduced density of NADPH-diaphorase-containing neurons in the corpus callosum in both genders (down to 52%) compared with the social control group. Furthermore, in the precentral medial cortex of female pups, a significant reduction in NADPH-diaphorase-reactive neurons (down to 72%) was detectable. All other regions of the medial prefrontal cortex and the nucleus accumbens remained unchanged. The observed deprivation-induced changes may reflect either an excessive reduction in NADPH-diaphorase-positive neurons or a down-regulation of the enzyme in neurons that normally express it.Our results indicate a link between early adverse socio-emotional experience and the maturation of NADPH-reactive neurons. Further studies are required to analyse the functional implications of this experience-induced brain pathology.     

Sex, but not repeated maternal separation during the first postnatal week, influences novel object exploration and amphetamine sensitivity

Sensation seeking and early life stress are both risk factors for developing substance use disorders. Neural adaptations resulting from early life stress may mediate individual differences in novelty responsiveness, and, in turn, contribute to drug abuse vulnerability. Animal models also demonstrate associations between novelty responsiveness or early life stress and increased sensitivity to psychostimulants. We investigated whether repeated maternal separation affects responses to novelty during adolescence and to amphetamine during adulthood, and whether maternal separation alters the relationship between these behavioral variables. Rat pups underwent separation (180 min/day) or control procedures (15 min/day) on postnatal days (PND) 2-8. Novel object exploration and amphetamine response were tested at PND 38 and 60, respectively. Adolescent males were less active in a novel environment and approached novel objects more frequently than females, but adult females showed greater amphetamine-induced locomotion. Maternal separation did not affect novelty responsiveness or amphetamine sensitivity. Locomotor activity in an inescapable, novel environment during adolescence predicted amphetamine-induced locomotor activity during adulthood in maternally separated rats, but not in controls. The results of this study suggest that adolescent responses to novelty may be particularly predictive of future substance abuse among survivors of early life trauma. Furthermore, sex differences in novelty and amphetamine responsiveness may complicate the relationship between these behavioral variables.     

Isolation distress and maternal comfort responses of two-week-old rat pups reared in social isolation

In 2-week-old rats, isolation from social companions in an unfamiliar place elicits ultrasonic vocalization rearing and locomotor behavior. These responses are prevented and close body contact is maintained if littermates or the dam are present. It has generally been believed that such isolation distress and comfort responses develop as a result of prior social experience. We reared pups in isolation from the third postnatal day and found essentially normal responses. A second experiment replicated and extended these results to pups reared in isolation from the day of birth. Isolation-reared pups did have higher levels of ultrasonic vocalization than their normally reared littermates, lower body weight, and lower post-test temperatures. We conclude that a lengthy period of close body contact and frequent social interactions with conspecifics are not necessary for the development of attachment responses in this species.     

The effects of sensitization and social isolation on maternal behavior in the virgin rat

Thirty-three out of 67 virgin Sprague-Dawley rats spontaneously retrieved 5–10-day-old foster pups in a pretest. The 34 rats not responding immediately were randomly divided into three groups to study the effects of direct and exteroceptive exposure to young on the induction of maternal behavior. Retrieving, licking and crouching behavior appeared in a higher proportion of cage rats (n = 12) which received a fresh group of pups to live with throughout each day than in control rats (n = 10) that had only 5 min daily exposure. However basket rats (n = 12) also became maternal merely by exposure to exteroceptive stimuli from pups living in baskets fixed to the cage wall. In a second experiment, virgin rats that spontaneously retrieved pups were socially isolated for 2–4 weeks. As a result, a 50–60% decrease in the number of rats showing retrieval was found not only in an independent sample of rats (n = 20) but also in a related group (n = 13) that practiced the response in the week between a pretest and Week 2 in isolation. Therefore, the results demonstrate that exteroceptive cues from pups alone may be sufficient to induce maternal behavior in nonspontaneously retrieving virgin rats, and that isolation from pups and other social stimuli reduce retrieving behavior in initially responsive virgin rats.     

Early social isolation of the domestic cat: Responses to separation from social and nonsocial rearing stimuli

The relative contributions of social-rearing stimuli (a mother and/or a littermate) and nonsocial-rearing stimuli (a brooder) to the formation and decline of infant kitten attachments were assessed by counting the frequency of distress cries produced by separation from the following rearing conditions: (1) mother-littermate; (2) mother-only; (3) brooder-littermate; and (4) brooder-only. Four male and 4 female kittens were reared in each condition. Each kitten was separated from its rearing condition once a week, from 2 until 5 weeks of age, and placed in open field for 15 min. The frequency of distress cries in both littermate-reared groups did not significantly differ throughout the experiment. The frequency was consistently high until 5 weeks of age when distress cries were significantly reduced. The frequency of distress cries consistently increased in the mother-only-reared kittens with repeated separations, but consistently decreased in the brooder-only-reared kittens. The results were interpreted as being commensurate with the social conditions at the time of separation.     

Protein kinase A activators produce a short-term,but not long-term,increase in respiratory-drive transmission at the hypoglossal motor nucleus in vivo

Synaptic plasticity is an intrinsic and conserved feature of neuronal activity that has been most extensively studied in the context of learning and memory in Aplysia and the mammalian hippocampus. However, the intracellular mechanisms underlying plasticity at motor nuclei, influencing motor behaviour, are less well studied. In vitro experiments in neonatal rodents indicate that protein kinase A (PKA) modulates respiratory-drive transmission at the hypoglossal motor nucleus (HMN), which innervates the genioglossus muscle of the tongue. We hypothesised that PKA activators at the HMN would increase genioglossus activity in vivo, whereas a PKA inhibitor would suppress activity indicative of constitutive PKA activation. Since PKA activators are importantly involved in models of long-term augmentation of neuronal activity following massed stimulation [16], we also hypothesised that application of PKA activators to the HMN would produce long-term facilitation of genioglossus activity. Experiments were performed in 25 isoflurane-anaesthetised, tracheotomised, spontaneously breathing adult rats. Microdialysis perfusion of 8-Br-cAMP (direct PKA activator) into the HMN increased genioglossus activity compared to baseline levels with artificial cerebrospinal fluid (P < 0.001). Application of forskolin (indirect PKA activator) had a similar effect (P < 0.002). Genioglossus activity progressively decreased back to baseline during a 90-min washout with artificial cerebrospinal fluid, demonstrating a lack of long-term facilitation of genioglossus activity. Similar to massed application of 8-Br-cAMP to the HMN, intermittent application produced a short-term (P < 0.001), but not long-term, increase in genioglossus activity in vivo. Application of Rp-8-Cl-cAMPS (PKA inhibitor) did not decrease genioglossus activity, indicating a lack of constitutive PKA activation.     

幼鼠中枢神经系统FOS蛋白表达升高与母婴分离相关

 目的 探讨幼鼠中枢神经系统下丘脑室旁核(PVN)及前皮质扣带回(ACC)内FOS蛋白表达与母婴分离(MS)的相关性。方法 按析因设计,32只SD新生大鼠分成4组,每组8只。A1B1组、A1B2组均为MS组,A1B1组在6周龄时接受结直肠扩张刺激(CRD),A1B2组在6周龄时未给予CRD;A2B1组、A2B2组均未给予MS,同为对照组,A2B1组在6周龄时接受CRD,A2B2组在6周龄时未给予CRD。A1B1、A2B1组幼鼠在接受CRD刺激后2 h和A1B2、A2B2组幼鼠一起处死。之后采用SABC免疫组化法检测不同脑区（包括PVN和ACC）内FOS蛋白免疫阳性（FLI）细胞表达情况。结果 新生期MS和幼鼠在6周龄时接受CRD刺激均可使PVN内FLI细胞数显著升高(F分别为7.033、35.212,P＜0.01)。也均使ACC内FLI细胞数显著升高(F分别为22.745、15.106,P＜0.01);两者对FOS蛋白表达的影响无交互作用。结论 幼鼠中枢神经系统（PVN和ACC）FOS蛋白表达升高与新生期MS明显相关。     

Dopamine antagonists produce an age-dependent increase in the responding of the young chick

In three experiments the effects of dopamine receptor antagonists on response-contingent punishment and autoshape learning of 1- and 4-day-old chicks were determined. In the first two experiments, 1- or 4-day-old chicks (N = 120) were trained to key-peck for heat reward and then injected intraperitoneally (ip) with either haloperidol (1.5, 2.5, or 5.0 mg/kg) or saline (Experiment 1) and with either haloperidol (2.0 mg/kg), sulpiride (50 mg/kg) or saline (Experiment 2) 30 min before a 96-trial response-contingent punishment session. In Experiment 3, 1- and 4-day-old chicks (N = 48) were injected ip with saline or haloperidol (2.0 mg/kg) 30 min prior to a 30-trial autoshape learning session. In both the punishment and appetitive tasks 1-day-old chicks pretreated with either haloperidol (1.5 to 2.5 mg/kg) or sulpiride showed a significant increase in key-peck responding compared with their saline injected controls. In contrast, 4-day-old chicks given either haloperidol (2.0 mg/kg) or sulpiride did not differ significantly from saline treated chicks on the punishment task, and on the autoshape task haloperidol-treated 4-day-old chicks responded on fewer trials than did their saline controls. These results indicate that dopaminergic synaptic transmission in the young chick as measured by dopamine D2 receptor blockers is functionally different at 1 compared with 4 days of age.     

Neonatal maternal separation in male rats increases intestinal permeability and affects behavior after chronic social stress

Prolonged maternal separation in rats has several effects on health and behavior. Here we investigated how maternal separation might interact with social stress in adulthood on behavior and gastrointenstinal permeability. The effects of either daily 180 min long term pup-dam separation (LMS) during the stress hyporesponsive period or daily 10 min brief maternal separation (BMS) on behavior, corticosterone and intestinal permeability were investigated, compared to a non-handling (NH) condition in male offspring. The animals from each separation condition were then randomly assigned to adult stress and control conditions, where the stress condition was exposure to 14 days of social instability (CSI). Sucrose preference, elevated plus maze behavior and corticosterone were measured. Colitis was experimentally induced by dextran sulfate sodium for 7 days, followed by measurement of intestinal permeability using the (51)CrEDTA method. Granulocyte marker protein was measured in feces and colons were examined histologically for inflammation. Prior to the social stress, the LMS offspring showed elevated corticosterone levels, lower elevated plus maze activity and less fluid consumption. After social stress, corticosterone levels were suppressed in LMS animals and again they showed less fluid consumption. LMS animals had significantly higher intestinal permeability, but only when also exposed to the social stress in adulthood. The current results support a two-hit model, whereby early life events interact with adult life events in altering animals' vulnerability.     

Neonatal maternal separation in male rats increases intestinal permeability and affects behavior after chronic social stress

Prolonged maternal separation in rats has several effects on health and behavior. Here we investigated how maternal separation might interact with social stress in adulthood on behavior and gastrointenstinal permeability. The effects of either daily 180 min long term pup-dam separation (LMS) during the stress hyporesponsive period or daily 10 min brief maternal separation (BMS) on behavior, corticosterone and intestinal permeability were investigated, compared to a non-handling (NH) condition in male offspring. The animals from each separation condition were then randomly assigned to adult stress and control conditions, where the stress condition was exposure to 14 days of social instability (CSI). Sucrose preference, elevated plus maze behavior and corticosterone were measured. Colitis was experimentally induced by dextran sulfate sodium for 7 days, followed by measurement of intestinal permeability using the ⁵¹CrEDTA method. Granulocyte marker protein was measured in feces and colons were examined histologically for inflammation. Prior to the social stress, the LMS offspring showed elevated corticosterone levels, lower elevated plus maze activity and less fluid consumption. After social stress, corticosterone levels were suppressed in LMS animals and again they showed less fluid consumption. LMS animals had significantly higher intestinal permeability, but only when also exposed to the social stress in adulthood. The current results support a two-hit model, whereby early life events interact with adult life events in altering animals' vulnerability.     

Environmental enrichment alters plus maze, but not maternal defense performance in mice

Maternal defense behavior (or maternal aggression) is a highly conserved behavior for protecting offspring that is normally associated with decreased fear and anxiety in rodent dams. Environmental enrichment can decrease indices of fearfulness and anxiety (and elevate novelty seeking) in laboratory animals. This study examined whether enrichment could alter levels of maternal aggression and elevated plus maze performance in lactating mice. One group of female mice was exposed to a series of novel objects for 1.5 months while the other group was not. As expected, mice that had been exposed to an enriched environment showed significantly more entries to and time on the open arms of an elevated plus maze while they were lactating. Enriched mice showed similar maze performances when tested 3 months later in a non-lactating state, even though enrichment had been removed for 3 months. Further, offspring of enriched dams exhibited maze performance similar to that of their dams, suggesting possible epigenetic influences on maze performance. In contrast, no differences in measures of maternal aggression or pup retrieval were detected between enriched and control lactating mice. Together, these results indicate that environmental enrichment has long lasting effects on plus maze performance, but does not alter maternal aggression. The findings also suggest that whatever neural pathways are altered by enrichment do not strongly overlap or regulate those governing maternal aggression.     

Pentoxifylline attenuates LPS-induced bronchial hyperresponsiveness but not the increase in exhaled nitric oxide

Background Inhaled endotoxin (LPS) may cause a transient increase in airway responsiveness, possibly through a cytokine-mediated airway inflammation, which is associated with an increase in nitric oxide synthesis and release. Objective We wondered whether pentoxifylline (PTX), which may attenuate cytokine release induced by LPS. could inhibit LPS-induced increase in airway responsiveness. Objective Methacholine (Mch) bronchial responsiveness was assessed 2 and 24 h after saline or LPS inhalation in eight subjects with bronchial hyperresponsiveness (PD20FEV1 610 ± 53 μg), treated with iv saline or PTX, in a double-blind crossover design. Nitric oxide (NO) in the exhaled air, which was expected to increase after LPS inhalation, and PEFR values were also measured at baseline, hourly for 6h and 24 h later. Results After LPS inhalation PEFR decreased significantly compared with placebo inhalation, reaching a maximum decrease of 11.25 ± 1.05 and 4.5 ± 0.84% of baseline, at 2h, respectively during saline and PTX infusion, P < 0.001. Exhaled NO were elevated after LPS compared with placebo inhalation at 1h (35.6 ± 4.8 vs 18 ± 2.8 ppb, P < 0.001), with no difference during saline or PTX infusion. Exhaled NO remained elevated until the 6th hour. PD20FEVI 2h after LPS inhalation was significantly lower than after placebo inhalation both during saline infusion (234 ± 29 vs 625 ± 62 μg, P < 0.001) and during PTX infusion (441 ± 47 vs 616 ± 48 μg, P < 0.001), the difference between saline and PTX being significant (P < 0.01). At 24 h no difference in PEFR, PD20FEV1 and exhaled NO was observed in comparison with pre-study values. Conclusion PTX attenuates both the decrease in airway patency and the increase in bronchial responsiveness induced by LPS inhalation, without any significant change in exhaled NO, which is increased by LPS inhalation.     

Fatigue varies by social class in african americans but not caucasian americans

Socioeconomic status explains many ethnic disparities in health; however, mechanisms are hard to identify. Fatigue—a frequent complaint in patients and normals—is associated with poorer quality of life. We wondered if ethnicity and social class interact to explain fatigue. A total of 40 African Americans (AAs) and 64 Caucasian Americans (CAs) completed short forms of the Profile of Mood States (POMS-SF) and Multidimensional Fatigue Symptom Inventory (MFSI-SF). Participants were divided into high-middle and low social class groups (as per Hollingshead, 1958a). After controlling for gender, body mass index, depressive symptoms, and response bias, ethnicity and social class interacted for POMS-SF fatigue. AAs in the high-middle classes reported more fatigue than AAs in the low classes and CAs in the high-middle classes. Fatigue did not differ by class for CAs nor by ethnicity in the lower classes. Similar findings emerged for MFSI-SF general fatigue. Social class is important for understanding fatigue in AAs but not CAs. This work was supported by National Institutes of Health grants HL36005 and RR00827.