bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety pharmacology program for pharmaceuticals
Authors: Kinter Lewis B. , Dixon Lon W.
Published: January 2005

Safety pharmacology data is used by clinicians, toxicologists, discovery scientists, and regulators involved in developing and registering new pharmaceutical products. We recently developed a safety pharmacology program to meet the needs of these diverse customer groups at Sterling Winthrop. We identified three classes of safety pharmacology studies: Core (cardiovascular, respiratory, renal, and CNS), having the broadest value to all customers; Special (ocular, auditory, etc.), occasionally needed to address compound or class effects; and Ancillary (GI, autonomic, behavioral), needed to complete international registration requirements. We established a tiered approach to the conduct of these studies that is efficient and cost‐effective, and developed general guidelines for designs of Core studies. The proposed program meets or exceeds all international regulatory requirements and insures that the necessary results are available for each customer group within the time frame that the data are most useful. © 1995 Wiley‐Liss, Inc.
Animal models of dementia
Authors: Porsolt Roger D. , Roux Sylvain , Wettstein Joseph G.
Published: January 2005

The major use of animal models for dementia is in the development of new therapeutic drugs. In contrast to other areas in psychopharmacology, where the predictive validity of animal models can be established by examining their response to known therapeutic agents, the search for antidementia drugs is hampered by the absence of recognized clinically effective reference compounds. Research scientists are therefore obliged to validate their models in terms of their similarity to the clinical condition. A second problem is the therapeutic target. Although antidementia drugs are intended to improve cognition in a general sense, the foremost therapeutic targets are the deficits in memory and attention associated with aging. The aging animal would appear to represent the best available model providing it can be shown that the cognitive deficits observed are similar to those observed in old age in humans. A logical consequence of this approach is to validate other experimental models in terms of their resemblance to naturally occurring age‐related impairments.

To illustrate these points, this paper reviews data obtained in aging animals in various behavioral models and the effects of drugs thereon. Comparisons are made between drug effects in aged animals with those observed in experimental models in young animals in which cognitive deficits are induced by anticholinergic drug treatment or lesions to cholinergic‐rich brain regions. It is concluded that aging induces cognitive deficits mainly associated with short‐term memory but that other aspects of cognition, namely attention and information processing speed, also decline with age. Putative antidementia drugs, particularly those facilitating cholinergic transmission, appear frequently to have more marked effects in experimental deficit models than in aged animals themselves. © 1995 Wiley‐Liss, Inc.
Anthrones, naturally occurring competitive inhibitors of adenosine‐triphosphate‐citrate lyase
Authors: Oleynek Joseph J. , Barrow Colin J. , Burns Michael P. , Sedlock David M. , Murphy Dennis J. , Kaplita Paul V. , Sun Hao H. , Cooper Raymond , Gillum Amanda M. , Chadwick Christopher C.
Published: January 2005

Adenosine triphosphate (ATP)‐citrate lyase (ACL) is a homotetrameric liver enzyme which catalyzes the cytosolic formation of acetyl‐CoA. This reaction provides the major source of acetyl‐CoA for fatty acid and cholesterol biosynthesis. Inhibition of ACL offers a potentially unique way to control plasma cholesterol and triglyceride levels. In this study, we describe the activity of an active microbial metabolite derived from a soil fungus, Penicillium sp., SC2193. This culture produces a series of related anthrones and anthraquinones. We present evidence for one of these anthrones, 2‐chloro‐1, 3, 8‐trihydroxy‐6‐methyl‐9‐anthrone, as a specific and competitive inhibitor of ACL against the substrate Mg citrate and mixed noncompetitive inhibition against two other required substrates for this enzyme, Mg ATP and CoA. With an IC50 of 283 nM in the primary assay and, more specifically, a Ki of <100 nM against the substrate Mg citrate, SC2193 represents the most potent competitive inhibitor of ACL yet described, and, as such, might prove very useful as a molecular tool for the discovery of selective, mechanistically novel hypolipidemic agents. © 1995 Wiley‐Liss, Inc.
Antinociceptive effects of a novel dual cyclooxygenase/5‐lipoxygenase inhibitor (tepoxalin) and its primary (carboxylic acid) metabolite (RWJ 20142) in acute tests in mice and rats
Authors: Raffa Robert B. , Connelly Charlene D. , Martinez Rebecca P. , Schupsky James J. , Argentieri Dennis C. , Singer Monica M. , Smith Ian L.
Published: January 2005

Tepoxalin is a novel dual inhibitor of cyclooxygenase (CO) and lipoxygenase (LO) pathways of arachidonic acid metabolism with a relative lack of gastrointestinal side effects within its preclinical therapeutic dose range. The present study investigated the antinociceptive action of tepoxalin and its primary (carboxylic acid) metabolite (RWJ 20142) in several acute tests in mice and rats. Tepoxalin produced dose‐related, non‐opioid (i.e., naloxone‐insensitive) antinociception in the mouse acetylcholine (ACh) induced abdominal irritant test (AIT) with an onset within 15 min and an exceptional duration (about 12 h). The oral ED50 value at peak effect (30 min) was 0.3 mg/kg (0.8 μmol/kg), compared to 0.9, 38.0, and 164 mg/kg (2.5, 160.8, and 1, 085 μmol/kg), respectively, for indomethacin, zileuton, and acetaminophen. Tepoxalin was inactive via intracerebroventricular (i.c.v.) administration (up to 200μg) or (up to 100mg/kg [259 μg/kg] p.o. or s.c.) in the endothelin‐1 (ET‐1) AIT and mouse 48°C hot‐plate tests. RWJ 20142 (a CO inhibitor), produced dose‐related, non‐opioid antinociception in the ACh test following oral (ED50 = 0.3 mg/kg [0.8 μmol/kg] at 30 min) or i.c.v. administration (ED50 = 3.3 μg [0.1 μmol] at 15 min) and was active p.o. in the phenyl‐p ‐quinone (PpQ) (ED50 = 0.2 mg/kg [0.6 μmol/kg] at 30 min) and ET‐1 tests (ED50 = 19.6 mg/kg [54.9 μmol/kg] at 30 min). It was the only compound active p.o. in the 48°C hot‐plate test and was significantly more potent than tepoxalin in the rat air‐induced AIT. Measurement of plasma levels suggests RWJ 20142 might be a major contributor to tepoxalin‐induced antinociception. The inactivity of tepoxalin in the ET‐1 test suggests a separate antinociceptive action of the parent compound. In summary, it appears that both tepoxalin and its primary metabolite contribute to tepoxalin‐induced antinociception in rodents, possibly by different mechanisms or at different sites, i.e., peripheral vs. central. © 1995 Wiley‐Liss, Inc.
Synergistic antinociceptive interaction between aspirin and tramadol, the atypical opioid analgesic, in the rat
Authors: Salazar L. A. , Martínez R. Ventura , López‐Muñoz F. J.
Published: January 2005

In order to assess a possible synergistic antinociceptive interactions, the analgesic effects of aspirin per s̀s (acetyl salicylic acid or “ASA”), a nonsteroidal anti‐inflammatory drug (NSAID), and tramadol s.c. (TRA), an atypical opioid analgesic, administered either separately or in combination were determined in a model of pain‐induced functional impairment in the rat, groups of six rats received either vehicle, ASA (175.4, 312.1, 555.1, 987.0, 1, 755.3, or 3, 121.2 μmol/kg) and TRA (21.3, 38.0, 67.5, 120.0, or 213.5 μmol/kg), or a combination of ASA and TRA (24 different combinations). This allowed us to detect the interaction profile of these combinations. The ED50 for either ASA or TRA were 1, 173.5 ± 7.4 μmol/kg and 141.5 ± 6.8 μmol/kg, respectively. The data obtained confirmed an interaction between ASA and TRA and showed antinociception that may be additive or synergistic, depending on the drug ratio administered. Furthermore, eight combinations showed various degrees of potentiation (P < .01), whereas the others (16) exhibited analgesic effects not different from that of ASA alone. The combination of ASA (3, 121.2 μmol/kg) and TRA (120.0 μmol/kg) produced the maximum analgesic effect. However, the combination of ASA (987/ μmol/kg) with TRA (120.0 μmo/kg) produced the highest potentiation effects. This study clearly showed (1) that there is an interaction between ASA and TRA and (2) which combination of these analgesic drugs produced either the maximum analgesic effect or the highest degree of potentiation in the rat. © 1995 Wiley‐Liss, Inc.
Effects of metrifonate and tacrine in the spatial morris task and modified irwin test: Evaluation of the efficacy/safety profile in rats
Authors: Blokland Arjan , Hinz Volker , Schmidt Bernard H.
Published: January 2005

In the present study we investigated the efficacy/safety profile of the cholinesterase inhibitors metrifonate (MTF) and tacrine [tetrahydroaminoacridine (THA)]. We tested the efficacy of MTF (12, 39, and 120 μmol/kg po) and THA (1.3, 4.3, and 13 μmol/kg po) in the spatial Morris task in 19‐month‐old rats. The modified Irwin test was used to evaluate the safety of both drugs, using in 19‐month‐old rats. In this observation test, higher doses of MTF (39, 120, and 390 μmol/kg) and THA (4.3, 13, and 43 μmol/kg) were tested. MTF was found to improve the performance of rats in the spatial Morris task. Independent of dose, MTF‐treated rats performed better than vehicle‐treated rats in the Morris task during the 2nd week of testing. THA treatment (1.3 μmol/kg) had only a minor effect on the spatial discrimination performance, i.e., effect on the probe trial after 2 weeks of training. In the modified Irwin test, both MTF and THA dose dependently induced side effects which were classified as being typically cholinergic. The threshold dose for the occurrence of side effects for acutely administered MTF and THA was 39 and 4.3 μmol/kg, respectively. Remarkably, repeated administration of 390 μmol/kg MTF (5 day treatment) resulted in fewer side effects. This was not observed for THA treatment. The data of the present study indicate that the efficacy/safety profile of MTF is more favorable than that of THA. © 1995 Wiley‐Liss, Inc.
Maternal and infantile influences upon exploratory behavior and emotional reactivity in the albino rat
Authors: Porter Richard H. , Wehmer Francine
Published: January 2005

A 2 × 2 × 2 factorial experiment was conducted to investigate the combined effects of maternal infantile handling, maternal pregnancy (offspring pre‐natal) stress, and offspring infantile handling on adult open‐field behavior and weight of albino rats. The primary results are as follows: (1) both offspring infantile handling and maternal pregnancy stress tend to increase adult exploratory behavior; (2) adult weight was lower for subjects whose mother had undergone stress during pregnancy than for offspring of non‐stress females; (3) several 2‐way interactions were found to significantly influence open‐field exploration; (4) when offspring infantile handling was combined with maternal pregnancy stress, emotional reactivity (i.e., defecation) was found to increase significantly over that following either type of stimulation alone.
Primacy of the negative aftereffect over positive adaptation in prism adaptation with newly hatched chicks
Authors: Rossi Patrick J.
Published: January 2005

Negative afteraffects (NAE) to prism displacement should not exist without prior positive adaptation (PA) during initial prism exposure. In 4 experiments, chicks wearing hoods containing 8.5° wedge prisms from the day of hatching showed: (a) significant NAE (pecking overcompensation in the direction opposite to their initial displacement error when matched O‐degree clear plates were substituted for the prisms), but not significant PA (reduction in the lateral error of pecking while wearing the prisms) at the sixth day; (b) NAE exceeding the theoretically predicted PA on the sixteenth day; (c) significant short and long duration NAE, and significant short and long duration reversal overcompensation effects (ROE) (left‐right pecking asymmetry following reversal of the prism base directions) on the seventh and eighth days, without prior PA on the seventh day; (d) neither significant NAE nor significant PA on the fourth day. Both significant NAE and significant PA had been reported previously on the eighth day. Geometrical analyses suggest that variables latent in unrestricted application of adult sensory rearrangement techniques to rapidly growing chicks of low sensory‐motor plasticity produce an ontogenetic‐development‐related reciprocity paradox.
Transfer of a learned form discrimination in the infant and adult monkey
Authors: Zimmermann Robert R.
Published: January 2005

Eight infant monkeys with a mean age of 67 days, range 50 to 84, and 8 adult monkeys were trained to discriminate an equilateral triangle from a circle. After reaching the criterion of learning, they were subjected to a series of transfer tests containing 20 different stimulus pairs. The groups did not differ significantly in rate of learning or transfer scores. Adults showed significant interproblem transfer to stimuli that had high generalization scores in other studies. Significant transfer was found to outline figures, intensity reversal and no consistent effect in responses to the sides of the triangle as opposed to the angles appeared.
Texture density and normal development of visual depth avoidance
Authors: Karmel Bernard Z. , Miller Patricia N. , Dettweiler Lawrence , Anderson Gary
Published: January 2005

Kittens, dutch‐belted rabbits, and albino rabbits were tested daily after eye opening for development of a reliable avoidance response on the visual cliff under varying conditions of texture density of elements comprising the checkerboard patterns of deep and shallow surfaces. Depth avoidance was demonstrated at an earlier age when coarse (34° to 18° retinal angle) rather than fine (2° or less of retinal angle) elements comprising shallow and deep surfaces were available to the subject. Visually guided placing to surfaces (in cats) developed after onset of visual cliff depth avoidance when coarse texture elements, but not when fine texture elements were used. Differences in onset of depth‐avoidance responding under different conditions of texture density across species as well as non‐coincidence of onset of visual placing with depth avoidance in cats indicated that changes in texture‐processing abilities with age and as a function of species characteristics interact with developing visual‐motor responding. The results were interpreted relative to organismic development of texture‐processing systems affecting degree of degradation of primary visual input during development. The importance of texture‐derived afferent information on development of visual‐motor behaviors was discussed.
Effects of maternal mobility, partner, and endocrine state on social responsiveness of adolescent rhesus monkeys
Authors: Anderson Clark O. , Mc Kenney Ann M. , Mason William A.
Published: January 2005

The social behavior of rhesus monkeys raised for the 1st year of life with mobile (MS) or stationary (SS) cloth surrogate mothers was investigated when the animals reached 4–5 yr of age. The MS males generally refrained from social interaction during initial pairings with females, whereas SS males interacted frequently, but were more often the targets of attacks and chases from adult females than were MS males. The MS males were more likely to vary their social behavior according to the behavior of the social partner and seemed to benefit more from extended social exposure than their SS counterparts. The MS females were more similar to wild‐born females than were SS females in nearly every behavior category and dimension tested. These results suggest that rearing with mobile artificial mothers improves the chances of later adaptive social adjustments in socially restricted monkeys.
Early environmental influences on conditioned and unconditioned ingestional and locomotor behaviors
Authors: Domjan Michael , Schorr Rebecca , Best Michael
Published: January 2005

For 34–44 days after weaning one group of rats was raised in a socially enriched environment, whereas another group was raised in isolated individual cages without handling. Following this differential rearing subjects were tested for ingestional neophobia and its attenuation, enhancement of ingestional neophobia by aversive drug administration, taste‐aversion learning and extinction, open‐field activity, and passive shock‐avoidance learning. Although the differential rearing influenced open‐field activity and shock‐avoidance, this manipulation did not have a significant effect on the various measures of conditioned and unconditioned ingestional behaviors. The results provide further evidence for the distinctiveness of gustatory‐visceral and telereceptor‐cutaneous sensory systems.
Long‐term effects of obstetrical anesthesia on infant autonomic function
Authors: Brackbill Yvonne
Published: January 2005

The results of this study suggest that anesthetics administered to mothers during delivery affect infants' autonomic function for at least 8 postnatal months. Under repeated auditory stimulation, those infants born without medication tended to show heart rate deceleration (orienting reflex) whereas those born under medication shifted from initial deceleration to acceleration (defense reflex).
Postweaning environmental stimulation and somesthetic performance in rats sustaining cortical lesions at maturity
Authors: Finger Stanley
Published: January 2005

Rats were enucleated at 28 days of age and were assigned to complex or relatively barren tactile environments for the duration of the experiment. Approximately half of the animals in each group received large, bilateral lesions of the somatosensory cortex when they were 60 days of age, and the remainder underwent sham operations. Twenty days later all groups were tested for the ability to master a series of tactile discriminations. Statistical tests revealed a highly significant lesion effect, but no environment or lesion x environment interaction effects. These sensory discriminative findings stand in contrast to some earlier reports which have shown that environmental complexity provided prior to or following other forebrain lesions can minimize error scores on simple learning tasks.
Female mouse maturation: Effects of excreted and bladder urine from juvenile and adult males
Authors: Drickamer Lee C. , Murphy Robert X.
Published: January 2005

A sequence of 4 experiments examined the effects of prepubertal and adult males on the sexual maturation of young female house mice. The results support 3 conclusions: (1) the presence of a prepubertal male or of urine from prepubertal males does not affect the timing of sexual maturation in young female house mice; (2) the maturation‐accelerating pheromone produced by adult males is present in the bladder urine of intact adult males but is absent from both excreted and bladder urine of castrated males; and (3) young females caged with 7 prepubertal males or with a castrated adult male mature earlier than control females caged alone. Results indicating that the presence of a castrated male leads to earlier sexual maturation of young female mice differ from previous findings. A possible explanation for this contradictory result is based on the ability of young weanling female mice to acclimatize and thermoregulate when separated from the dam and litter‐mates. A model for density‐feedback population regulation in house mice involving pheromones produced by males and females is presented.
Neonatal stimulation, maternal behavior, and accelerated maturation in BALB/c mice
Authors: Cross Michael S. , LaBarba Richard C.
Published: January 2005

An experiment was conducted to examine the effects of neonatal handling and hypothermia on infant physical maturation and growth and on maternal behavior in BALB/c mice. Stringent methodological and statistical controls were employed for experimenter bias and litter effects. No evidence appeared to support claims that neonatal stimulation leads to accelerated physical maturation. Alterations in maternal behavior patterns were found only immediately following hypothermia of pups. Maternal behavior did not correlate highly with offspring maturational rates, but maternal weight and age and pup birth weight were highly predictive of infant physical maturation.
Ontogeny of two‐way avoidance in male and female rats
Authors: Bauer Richard H.
Published: January 2005

In Experiment I, 17‐, 21‐, 36‐, 51‐, 90‐, and 200‐day‐old male and female rats were given a single session of 100 two‐way avoidance (TWA) trials. In the 2nd experiment, males and females of these ages and 15 and 28 days of age that were obtained from a different source, weaned at a later age, and housed differently received TWA training. Results of both studies showed that avoidance of 15‐, 17‐, and 21‐day‐old rats is low, but avoidance increases from 21 to 51 days of age. Avoidance of 95‐ and 200‐day‐old animals was generally lower than 51‐day‐old rats. No significant gender differences appeared until 90 days of age; at this age avoidance of males was lower than females. In Experiment III, CS intensity was varied and the US intensity was lower than that used in Experiments I and II. Avoidance of 21‐ and 90‐day‐old rats was higher with a more intense CS, but 21‐day‐olds were still lower than adults. Avoidance of 17‐day‐old rats was not affected by CS intensity.
Effects of age and stimulus intensity of the far field auditory brain stem potentials in the laboratory mouse
Authors: Henry Kenneth R. , Haythorn Mark M.
Published: January 2005

The vertex‐positive, volume‐conducted far field response was used to evaluate age‐related changes of the 8th cranial nerve and auditory brainstem in the anesthetized C57BL/6 mouse. Responses were obtained from stimuli as low as 10 dB (within the 10‐20 kHz bandpass). When latencies were compared between 16‐ and 35‐day‐old subjects, the older mice had a P1 component which was .175 msec faster, a P2 which was .505 msec faster, a P3 which was .953 msec faster, and a P4 which was 1.315 msec faster. A retest of the younger mice showed that much of this retrocochlear latency decrease occurred between 16 to 18 days postpartum. The latencies of the younger mice were also less likely to decrease as the stimulus intensity was increased from 30 to 70 dB, and this effect was most pronounced at higher neural levels. These age‐related changes bear considerable relationship to the development of susceptibility of audiogenic seizures in the mouse.
Pituitary‐adrenal response to separation in mother and infant squirrel monkeys
Authors: Mendoza Sally P. , Smotherman William P. , Miner Martin T. , Kaplan Joel , Levine Seymour
Published: January 2005

Pituitary‐adrenal response in mother and infant squirrel monkeys following brief separation was assessed. Each mother and infant pair was tested under each of 3 conditions: (1) Basal; (2) Separation‐Reunion; and (3) Separation. Samples were obtained from mothers and infants in the Separation and Separation‐Reunion conditions 30 min following the initial disturbance. A similar paradigm was used to assess the effects of separation in surrogate‐reared animals. The results indicate that mothers, infants, and surrogate‐reared infants respond to 30‐min separation with a substantial increase in plasma cortisol. The values obtained in the Separation‐Reunion condition did not differ significantly from Basal values in any of the 3 groups, suggesting that the effect of separation on the pituitary‐adrenal system is not due to the disturbance involved in the separation procedure. The response of surrogate‐reared infants suggests that these infants develop similar attachments to the surrogate as normal infants to their own mothers.
A comparison between the models of the psychological refractory period proposed by Welford and Surwillo and Titus
Authors: Smith Glen A.
Published: January 2005

A model of the psychological refractory period (PRP) proposed by Surwillo and Titus (1976) is compared critically with that proposed by Welford (1952) noting the following points:

Surwillo and Titus augment the single channel hypothesis of Welford's model with other assumptions that are unnecessary as Welford's model fits their data (and the great bulk of other studies) with great precision.

An anomaly overlooked in their application of the model to the data was found, namely, a counterintuitive decrease in reaction time to the 2nd stimulus below its asymptotic value. This has not been reported in any PRP data. The assumption in error is pointed out and a correction suggested.

When an essential expansion of their model to incorporate varying signal processing times is made, the notion of an inert Recovery Period used by Survillo and Titus becomes redundant. If this is discarded on grounds of parsimony, the major remaining difference between the models is Surwillo and Titus' additional restrictive assumption of discrete time segments gated by an EEG rhythm for which their data do not present any strong evidence.

Although Welford's model is limited for developmental data as it only fits, rather than predicts, increases in reaction time with development, it is more accurate and preferable. Investigations of more cognitive variables such as practice may produce better explanations of developmental changes in reaction time than will measurement of small concomitant changes in physiological time parameters.
Effects of differential early experience upon parental behavior in Mus musculus
Authors: Bell Robert W. , Little Jill
Published: January 2005

Infant mice reared with both parents were subjected to 1 of 4 different early experience contingencies at 3, 6, 9, and 12 days of age. Observation of parental behaviors following return of the pups to the nest revealed that mothers attended more to pups subjected to intermediate levels of stress, with the differences in maternal behavior persisting across the age span without change. Fathers exhibited marked changes in responsiveness to young across the ages observed, with their attention to young correlating directly with rate of ultrasonic calling by the young.
Locomotor activity and social behavior of old rats after preweaning undernutrition
Authors: Schenck P. E. , Koos Slob A. , Van Der Werff Ten Bosch J. J.
Published: January 2005

Rat pups were undernourished from birth to 25 days of age by giving them a nipple‐ligated mother and a normal lactating mother for alternate periods of 12 hr/day, thus providing adequate full‐time maternal care. Male and female rats undernourished neonatally had greater locomotor activity than controls in old age (16–20 months). Females were more active than males, irrespective of neonatal undernutrition. At the age of 24 months, social behavior was recorded at various times of the day for pairs of male rats (1 previously undernourished and 1 control). With one minor exception, undernourished animals did not differ significantly from controls in the incidence of the various behavioral items that were scored. Neonatal social factors may compensate for possible negative effects of neonatal undernutrition on later social behavior.
Spontaneous pup‐killing by mice in response to large litters
Authors: Gandelman Ronald , Simon Neal G.
Published: January 2005

Primiparous lactating mice whose young were removed on the day of parturition were presented with foster litters of either 12 or 16 day‐old young. The adults spontaneously killed young during Days 3‐7 of the lactation period, killing more in the 16‐pup than in the 12‐pup litter. The lactating animal appeared to select the young to be killed on the basis of body weight. It killed significantly more young that were in the bottom half than in the top half of the weight range for its particular litter.
Ontogeny of brain catecholamine turnover and susceptibility to audiogenic seizures in DBA/2J mice
Authors: Shaywitz Bennett A. , Yager Robert D. , Gordon Judith W.
Published: January 2005

We have investigated the relationship between catecholamine turnover and susceptibility to audiogenic seizures (AGS) in the developing DBA/2J mouse. Turnover of dopamine and norepinephrine was determined after administration of alphamethylparatyrosine at 3 weeks of age when nearly all mice (94%) exhibited AGS, at 6 weeks when only 30% were susceptible, and at 12 weeks when none developed seizures. Turnover of brain dopamine increased progressively from 236 ng/g/hr at 3 weeks to 389 ng/g/hr by 12 weeks of age. Norepinephrine turnover increased significantly between 3 and 6 weeks of age, then remained stable thereafter. Turnover times for each catecholamine did not change appreciably with maturation. Our results support the notion that susceptibility to AGS may be mediated in part by brain catecholaminergic mechanisms.
The role of diet in mother‐infant reciprocity in the spiny mouse
Authors: Doane Helen Marie , Porter Richard H.
Published: January 2005

One‐day‐old spiny mouse pups responded preferentially to bedding soiled by lactating conspecifies fed the same diet as their mothers. Following this test, pups were fostered onto different‐diet females. When retested at 84–96 hr of age, no preferences were shown for bedding soiled by a female fed the biological mother's diet vs bedding of a female fed the different diet. When tested again at 120–132 hr of age, however, the pups preferred the bedding associated with their foster mother's diet. In a 2nd experiment, recently parturient females retrieved 1‐day‐old pups born of same‐diet females faster than pups born to novel‐diet females. These results indicate that pup preferences for chemical cues produced by lactating conspecifics can be altered by sufficient exposure to a 2nd female maintained on a different diet and that neonatal chemical cues, like maternal chemical stimuli, are diet‐dependent.
Perinatal malnutrition and early handling: Interactive effects on the development of the pituitary‐adrenal system
Authors: Wiener Sandra G. , Levine Seymour
Published: January 2005

The preweaning development of the pituitary‐adrenal system was investigated in perinatally malnourished rodents. Malnourished pups that were routinely handled displayed an earlier plasma corticosterone stress response to electric shock and an accelerated development of feedback inhibition of the stress response by exogenously elevated steroid levels. Although malnourished pups displayed elevated basal corticosterone levels compared to well‐fed controls, the post‐stress levels were also higher in these malnourished young. Thus, the corticosterone response to stress was not impaired in malnourished pups.

The influence of the early handling of malnourished young on pituitary‐adrenal activity was also studied. Whereas the accelerated development of the stress response and the elevated post‐shock levels were not the result of early handling, the elevated basal corticosterone levels displayed by handled malnourished pups were not present in nonhandled malnourished pups. Thus, the early non‐nutritional environment interacts with malnutrition to alter the development of the pituitary‐adrenal system.
A method for artificial feeding of motherless 2‐week‐old rat pups
Authors: Ackerman Sigurd H. , Shindledecker Richard
Published: January 2005

When the rat mother is permanently removed from her litter at 14–15 days postnatally, weight loss in the pups routinely occurs. We now describe a method by which normal weight gain can be achieved at this age in the absence of the mother. Liquid flowing in a continuous stream down a glass surface in the home cage elicits spontaneous licking from the rat pups. If the liquid is a high fat milk formula, the rat pups maintain normal body weight. They do not maintain normal weight if low fat (bovine) milk is presented in this way or if the high fat milk formula is merely available in a reservoir on the cage floor.
Interactive effects of parity and early pup stress on the open field behavior of laboratory rats
Authors: Wright Linda , Bell Robert W.
Published: January 2005

Pups of primiparous and multiparous Sprague Dawley rats received 0‐, 2‐, or 5‐min cold stress on Days 2–6 postpartum. Stressed offspring of primiparous mothers had shorter latencies to move in an open field than did control offspring of primiparous mothers. However, stressed offspring of multiparous mothers had longer latencies than did the controls. The results suggest differences in maternal responsiveness immediately following return of stressed pups to the nest.
Body temperature and 5‐hydroxytryptamine during early postnatal maturation in mice
Authors: Goodrich Cecilie , Choy Marina
Published: January 2005

A relationship between the maturational increases in body temperature and brain indoleamines has been explored through altering brain 5‐hydroxytryptamine (5‐HT) content. Effects on body temperature at approximately constant ambient temperature (about 24°C) have been studied following pharmacological manipulations in mice up to 16 days postpartum. Administration of 5‐hydroxytryptophan (5‐HTP) to increase 5‐HT levels was associated with decreased body temperature throughout the maturational period. Depletion of 5‐HT with p‐chlorophenylalanine (p‐CPA) was associated with increased body temperature at all ages studied, although 5‐HT depletion was less effective in young animals than in older animals. The drug NSD‐1034 acts at a different enzymatic step, and is effective in both central and peripheral tissues to reduce 5‐HT and norepinephrine (NE) levels. NSD‐1034 decreased body temperature up to 10 days of age; however, the effect was reversed at about 14 days, and the drug increased body temperature significantly in 16‐day‐old animals. These results suggest a role for 5‐HT in the mechanisms of heat production in early postnatal life.
Differential extinction of 2‐way active avoidance in young and adult rats
Authors: Brennan James F.
Published: January 2005

Three experiments examined age‐related differences in extinction of active avoidance in rats through manipulation of the stimulus context. In Experiment I, 36 weanlings and 36 adults acquired comparable avoidance levels to a tonal conditioned stimulus (CS), and novel stimuli consisting of either the presence of a naive rat or a light were presented during 2 tests in extinction. Results indicated more pronounced disruption of extinction in the pups, compared to adults, with the animate novel stimulus having the greater effect. Eighteen pups of 22 days of age and 18 adults in Experiment II were trained to avoid shock with a CS consisting of simultaneous tone and light onset. During extinction responses did not terminate 1 of the CS elements, but rather produced continuation of either the tone or light for an additional 5 sec. Continuation of the tonal element resulted in greater disruption of extinction trials than the light in the adults, although the pups had faster, but nondifferential, extinction rates. A 3rd experiment presented 36 pups and adults with either 0‐, 5‐, or 10‐sec delays of tonal CS reactivation after extinction responses. Both 5‐ and 10‐sec delays resulted in increased numbers of extinction trials in the adults, but the pups failed to respond differentially to any of the delay intervals. Results of all of the experiments were considered in light of species‐specific behaviors in avoidance extinction relative to environmental and associative saliencies between ages.
Neonatal treatment of hamsters with barbiturate alters adult sexual behavior
Authors: Clemens Lynwood G. , Popham Teresa V. , Ruppert Patricia H.
Published: January 2005

Male and female hamsters were given 50 μg pentobarbital, 100 μg pentobarbital, or 100 μg d‐amphetamine on postnatal Days 2–4. When tested for masculine sexual behavior in adulthood, males treated with 100 μg pentobarbital showed behavioral deficits when tested with testes intact as well as after castration and treatment with testosterone propionate. Deficits shown by 50 μg pentobarbital males were overcome by testosterone replacement. When tested for feminine sexual behavior, males treated with 50 μg pentobarbital showed enhanced lordotic responses whereas males treated with 100 μg d‐amphetamine showed no differences from controls when tested for female sexual behavior or when tested for male sexual behavior. Drug treatments had no effect on adult masculine or feminine sexual behavior in neonatally treated females. The results of this study show that pentobarbital can inhibit normal masculinization of the male when given during behavioral sexual differentiation.
Ontogeny of the visual evoked response in the stump‐tailed macaque
Authors: Dustman R. E. , Snyder E. W. , Creel D. , Beck E. C.
Published: January 2005

Visual evoked responses (VER's) of stump‐tailed macaques were studied from birth to 80 weeks in an attempt to establish the utility of this species as a model of human neurophysiological development. Although human subjects and monkeys share a unique complexity of the VER at birth, the postnatal development of their VER's does not appear to follow a parallel sequence. The relatively dynamic nature of the VER during the 1st few weeks in a monkey's life may limit the usefulness of this species as a model of human development. The rapid changes in the VER of the developing monkey and the observation that these changes continue beyond 2 years of age should be considered in studies of the VER in which repeated measures are obtained over a prolonged period of time.
Behavioral effects of rotation between lactating and nonlactating females
Authors: Fleischer Susan F. , Turkewitz Gerald
Published: January 2005

Rat pups stunted by housing only 8 hr daily with lactating females and 16 hr with nonlactating foster mothers showed a delay in returning to their nest from other parts of the home cage. This delay was not due to changes in activity level or to lack of attraction to the nest, but appeared to be perceptual in nature. Both lactating and nonlactating females caring for stunted litters tended to be more maternal than those caring for control pups. After nutritional rehabilitation, the adult experimental animals showed no deficits in learning a series of visual discrimination problems in a modified version of the Lashley jumping stand procedure with a nonappetitive reinforcement. We compared the results with those obtained when other methods of stunting animals are employed and concluded that different methods of stunting may result in both common and divergent effects on behavior. Although many methods of stunting may produce similar behavioral deficits during the period of food deprivation, after rehabilitation behavioral deficits reported with other techniques of stunting may be due to extranutritional causes rather than to reduced food intake per se.
Spontaneous alternation in chicks using social reward
Authors: Cogan Dennis C. , Jones Jimmy F. , Irons Thomas
Published: January 2005

Two experiments examining spontaneous alternation in young white Leghorn chicks are reported. In Experiment I chicks (20 per group) run in a T‐maze for 4 trials to social reward displayed alternation of responses, whereas nonrewarded chicks did not alternate. In Experiment II socially rewarded chicks (20 per group) again showed reliable alternation of responses whereas food, water, and nonrewarded chicks did not alternate. These data support the premise that spontaneous alternation behavior has some phyletic generality under optimum conditions, although the mechanisms which control it may differ across species.
A minimal visual restriction experiment: Preventing chicks from seeing their feet affects later responses to mealworms
Authors: Wallman Josh
Published: January 2005

Chicks raised from hatching for 2 days without being able to see their feet because of cloth foot covers were less likely than controls to eat or pick up mealworms, which resemble the chicks' feet in some respects. Instead the chicks spent much time staring at the mealworms. Similar, but perhaps weaker, effects were obtained when the toes were simply painted black. These results may reflect processes of perceptual learning characteristic of infant animals.
Approach and departure patterns generated in the domestic chick by intermittent white light
Authors: Simner Marvin L.
Published: January 2005

Newly hatched domestic chicks were given extended free access to 7 rates of intermittent white light between .5 and 24 flashes per sec. Inspection of the data showed approaches and departures directed toward the light that increased in number and formed an orderly pattern as the rates neared 4 per sec and as the chicks exposed to this rate became older. Also, no differences were found in the amount of time chicks remained next to the various rates during each approach but only in the amount of time they remained away during each departure. The bearing of these results on the proposal that flicker phototaxis might stem from the neural excitation produced through photic driving was discussed along with relating further evidence to recent work in imprinting.
Home orientation in nursling rats: The effects of rehabilitation following intergenerational malnutrition
Authors: Galler Janina R.
Published: January 2005

Rat pups with histories of intergenerational malnutrition were rehabilitated by cross‐fostering at birth to well‐nourished females. These pups weighed slightly less than well‐nourished controls but significantly more than pups reared by malnourished females. Rehabilitated and control pups were both more active than malnourished pups reared by malnourished females. However, the percentage of nest returns by pups displaced to other parts of the cage was low among rehabilitated pups as compared with controls, but did not differ from that of pups with histories of intergenerational malnutrition reared by malnourished females. These data suggest that, although activity is a product of postnatal condition, home‐orienting behavior is affected by a history of intergenerational malnutrition regardless of rehabilitation.
Deficits in fixed‐interval performance following prenatal and postnatal lead exposure
Authors: Zenick Harold , Rodriquez Ward , Ward Jerry , Elkington Brian
Published: January 2005

Female rats were exposed daily to 750 mg/kg of lead acetate via a restricted watering schedule for 70–80 days prior to mating and then throughout pregnancy and nursing. At weaning, litters from half of the lead dams were placed directly on treatment for the duration of the experiment. These manipulations yielded 3 groups: Group Pb/Pb, offspring exposed during pre‐ and postweaning periods; Group Pb/C, offspring exposed only during preweaning periods: and Group C/C, control offspring. Beginning at 42–49 days of age, postnatal, offspring were shaped to bar press under a fixed‐interval, 1‐min schedule (FI1) and then given 20 sessions, each 45 min in length. Analyses revealed that Group Pb/Pb received fewer reinforcements across sessions than the other 2 groups, which did not differ. However, when the Pb/Pb offspring did receive reinforcement, they exhibited the scalloped pattern of responding characteristic of fixed‐interval schedules.
Sleep‐waking patterns in hypoxic kittens
Authors: Baker Theodore L. , McGinty Dennis J.
Published: January 2005

Kittens at 10, 20, and 40 days of age were made intermittently hypoxic in 10 or 7% oxygen chambers for either 3 or 8 days. Respiration, EKG, EEG, and neck and eye movements were recorded during hypoxia. Compared to 21% oxygen controls, hypoxic kittens had fewer and shorter epochs of active sleep, and longer epochs of quiet sleep. Some hypoxic kittens exhibited slow and labored respiration during quiet sleep and transitional epochs, which reversed during active sleep. Kittens that showed most pronounced respiratory changes or died had less active sleep than kittens that compensated adequately and survived. These results suggest that active sleep may be important for stimulation of respiration during infancy. Suppression of active sleep, augmentation of quiet sleep, or other disturbances to normal sleep‐waking patterns during hypoxia, may increase the risk for hypoxic respiratory depression and death.
Effect of handling on positive and negative contrast effects
Authors: Fagen Jeffrey W. , Rycek Robert F.
Published: January 2005

The effects of early handling on the exhibition of positive and negative contrast effects were investigated. Over two 4‐day testing sessions, animals were given alternating 1‐min access periods to 2 bottles containing either 32 or 4% sucrose solutions. Measures of lick rate and latency to switch bottles revealed that both handled and nonhandled animals exhibited contrast effects of equal magnitudes. The results did not support an emotional interpretation of contrast effects but were interpreted as support for the perceptual theory of this phenomenon.
Learned responses to movement in neonates
Authors: Evans Barrie
Published: January 2005

Numerous previous reports have pointed to the importance of movement (vestibular) stimulation in early infancy. Nevertheless, we have currently no clear understanding of these effects. The present paper looks at the role of movement stimulation in the modification of inborn organized patterns of response. Two laboratory experiments are reported in which newborn infants were presented with a cue (movement stimulus) which was either paired with dextrose presentation (experimental group) or not paired (control group). The experimental and control groups differed on the pattern of sucking in extinction, indicating an effect due to the contiguous presentation of movement and dextrose. Those experiments provide an analog for some naturally occurring conditions in early infancy and support some Soviet observations on the development of the earliest conditioned responses.
The ontogeny of nipple‐shifting behavior in albino rats: Mechanisms of control and possible significance
Authors: Cramer Catherine P. , Blass Elliott M. , Hall Warren G.
Published: January 2005

Nipple‐shifting behavior was studied in rats 3–‐30 days old in 4 experimental paradigms. The incidence of nipple‐shifting of rats tested in groups of 3 on their nonlactating, anesthetized mother was age‐related. Rats 12 days of age and younger did not leave the nipple first suckled during the 2‐hr test period. Starting by Day 15, however, nipple‐shifting increased and reached its maximum in 24‐day‐old rats. This behavior's incidence was directly related to maternal (and, therefore, nutrient and water) deprivation (Experiment I). Milk letdown reduced the incidence of nipple‐shifting behavior at all ages studied and synchronized its occurrence, as almost all shifts occurred immediately after letdown and almost none during the 15‐min interval between successive milk letdowns (Experiment II). Testing rats individually on the nonlactating, anesthetized mother produced age‐related effects. Shifting was virtually eliminated in 15‐day‐old rats, markedly reduced in 21‐day‐old rats, and not affected in 27‐day‐old rats tested individually (Experiment III). Rats 27 and 30 days of age, upon leaving a nipple, ate and did not return to suckle. Rats 15 days old never ate and always returned to suckle (Experiment IV). Twenty‐one‐day‐old rats suckled, and many ate in the mother's presence. The significance of these findings relates to maximizing milk intake and facilitating the process of weaning.