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One of the critical issues confronting the evolving discipline of behavioral and neurological toxicology is the general lack of test validation in animal models. This paper seeks to provide a strategy aimed at resolving this important problem. It is proposed that test validation be accomplished by evaluating known neurotoxins in a battery of tests chosen to assess in animal models a wide range of effects on the basis of reported human toxicosis symptomatology. We propose to measure ongoing home cage motor activity, food consumption, water consumption, clay consumption (and the diurnal cycling of these), neurological/physiological indices (reflexes, autonomic signs, equilibrium/gait, balance, tremor, reactivity, and muscular strength), and aspects of cognitive and associative behavior involving both endogenous and exogenous (sensory) control of responding. An integrated, time-efficient scheme, covering 90 days of chemical treatment and 30 days of post-dosing recovery will be used. Chemical substances to be evaluated were chosen with the view of representing classes of neurotoxic effects. For initial study, triethyltin was chosen as an agent producing demyelination of nerves, acrylamide as an agent producing "dying-back" neuropathy, and methylmercury as an agent producing mixed central and peripheral neuropathies. Agents which attack specific loci in the nervous system and those producing anoxia will not be assessed in the first stages of this research due to lack of species generality of known effects, present lack of appropriate exposure facilities, or other problems. In addition, two drugs (amphetamine and sodium salicylate) will be investigated to support the generality of the testing procedures. By comparing the observed results of the neurotoxins in the animal models with the predicted effects based on reported human symptomatology, some decision concerning the validity of each procedure will be made. It is expected that the validation of tests to be used in behavioral and neurological toxicology will permit the meaningful assessment of more complex issues, such as the mechanisms by which neurotoxins act.
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PMID:Strategy for the assessment of neurobehavioral consequences of environmental factors. 72 Mar 19

A comparison was made of the number of spontaneous cleaning reactions (washing, scratching, licking and shaking) in young rabbits from the seventh to 42nd day of life in different conditions: in the home cage, when first placed in the experimental chamber, after several repeated (daily) stays in the chamber, and after handling. It has been found that when first placed in the chamber the rabbits perform there significantly fewer cleaning reactions than in the home cage; while those which have repeatedly been in the experimental situation, perform considerably more cleaning reactions in the chamber than the intact rabbits of the same age in the home cage. The handled rabbits when they first get into the chamber, also exhibit more reactions than in the cage. This activating influence of early experience goes on for two to three weeks and is followed by habituation, and the number of cleaning reactions in the cage and in the chamber becomes equal. The results are discussed in terms of novelty of the environment, sensitization and habituation.
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PMID:[The influence of early experience on the development of cleaning responses in rabbits during ontogenesis]. 121 Jun 67

Male and female Mongolian gerbils (Meriones unguiculatus) carrying three coat color alleles, agouti, sandy, and black, were tested for 15 min under three cage temperature conditions, warm (35-40 degrees C), neutral (20 degrees C), and cold (0-5 degrees C). A frequency count of scratching, face and body wash, belly/side rubs, and shaking was taken of these animals' activities during the test sessions. Sex differences were not evident but coat color and age temperature affected the belly/side rubs and shaking activities. There were also effects of cage temperature but not coat color on face/body wash and scratching. It appears that animals with these coat color variants manifest disparate patterns of COBS behavior when encountering different thermal environments.
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PMID:Coat color genes and cage temperature effects on care of the body surface (COBS) behavior of Meriones unguiculatus. 159 Jul 29

The effects of maternal proximity on the behavioral and physiological responses of infant rhesus macaques during 4 days of total or adjacent separations from the mother were studied. The 6 infants tested showed behavioral responses that differentiated the two separation conditions. Major differences were found in the quantity and quality of vocalizations, the occurrence of cage-biting and cage-shaking behavior, object exploration, and hunched and freezing postures. In particular, the structure of coo vocalizations clearly discriminated between the presence or the absence of the mother during separation. Cerebrospinal fluid (CSF) concentrations of dopamine and serotonin metabolites did not discriminate between the two separation conditions but showed a transient elevation at 24 hr after separation and were not different from baseline by 96 hr after separation. In contrast, both the plasma cortisol and the CSF norepinephrine metabolite responses tended to be greater and to persist for a longer period of time when infants were totally isolated. The results are discussed within the context of attachment and coping theories.
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PMID:Influence of maternal proximity on behavioral and physiological responses to separation in infant rhesus monkeys (Macaca mulatta). 169 May 49

Fetal substantia nigra (SN) cells were transplanted into the caudate nucleus (CN) of four vervet monkeys (Cercopithecus aethiops sabaeus) that had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP treatment appears to produce a syndrome similar to that observed in patients with idiopathic Parkinson's disease. Normal and parkinsonian behaviors were quantitated by trained observers 5 days/week. Twenty-eight behaviors based on previous factor analyses were individually scored and rated. Parkinsonian signs included freezing, head and limb tremor, difficulty in eating, delayed initiation of movement, poverty of movement, tremor that stopped with intention, decreased response to threats, and lying immobile in the cage. These signs were combined to give an overall rating of parkinsonism. A summary measure of 'normal' healthy behavior was also examined, including such behaviors as yawning, scratching, self-grooming, shifting, and eating. Overall ratings of parkinsonism increased and those of healthy behavior decreased after MPTP. In the 4 monkeys grafted with fetal SN cells into the CN, behavior returned to pre-treatment levels by the time of sacrifice (2, 5, or 7.5 months after grafting). Three control subjects were transplanted with either SN cells into an inappropriate brain site (cortex) or inappropriate, non-dopaminergic, cells (cerebellar) into the CN. Subjects were also compared with three control animals that did not receive MPTP but received cryopreserved or fresh SN and other cells into the CN. Only MPTP-treated subjects that received SN cells into the CN showed evidence of a reversal of the MPTP syndrome after transplantation. In addition, grafting in animals that were not MPTP-treated did not appear to affect behavior. This paper reports the specific behavioral effects of severe MPTP toxicity that were or were not reversed after transplantation and suggests that only fetal SN cells grafted into the CN may be able to reverse behavioral deficits in MPTP-treated monkeys.
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PMID:Grafting of fetal substantia nigra to striatum reverses behavioral deficits induced by MPTP in primates: a comparison with other types of grafts as controls. 189 83

C57BL/6J mice were rendered physically dependent on morphine by giving them ad lib access to a drinking fluid containing 0.2% saccharin and morphine for 14 days at 20-22 degrees C. Core body temperatures were monitored by radio telemetry, which obviated the need for restraint, handling, or otherwise disturbing the animals. Consistent hyperthermia was present throughout the morphine intoxication phase, followed by hypothermia after the withdrawal syndrome had been precipitated by naloxone challenge (2.0 mg/kg, IP) at 22.5 degrees C. The hypothermia could be blocked by exposing the animals to a 34.5 degrees C ambient temperature, which also prevented the occurrence of tremor and "wet dog shakes." In contrast, the other withdrawal signs monitored were not significantly affected. In a second experiment, mice were given the same morphine-saccharin drinking fluid as before, except that a choice was provided between two interconnected home cages (23 degrees C vs. 35 degrees C) throughout the experiment. A marked preference for the 35 degrees C cage was seen during intoxication, which served to enhance the hyperthermia due to morphine. Following withdrawal, when hypothermia is evident, the preference for the 35 degrees C cage declined to control levels. These results suggest that hypothermia is both a consequence and a contributor to the opioid withdrawal syndrome.
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PMID:Components of the opioid withdrawal syndrome in mice are thermoregulatory responses. 262 79

The authors studied the response of 10 macaque monkeys to administration of sodium lactate, a panicogenic agent used in human panic disorder research, after treatment with the tricyclic antidepressant imipramine, the triazolobenzodiazepine alprazolam, or placebo. Both drugs effectively blocked the lactate-induced acute endogenous distress responses that had been reliably observed in the monkeys before drug treatment. Only alprazolam significantly reduced the occurrence of conditioned situational anxiety responses observed in the home cage. The alprazolam monkeys appeared to be sedated compared to the imipramine and placebo groups, and tremor and temporary exacerbation of anxious behaviors were observed during alprazolam withdrawal.
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PMID:Imipramine and alprazolam treatment of lactate-induced acute endogenous distress in nonhuman primates. 210 42

The aim of this study was to investigate the effects of a mechanical stressor and individual behavior differences (separately and in combination) on tumor development in the female Syrian hamster. Studies by other investigators have documented the tumor-enhancing effects of such mechanical stressors as rotational stress. Previous studies by our group found that both size of tumor and time to tumor detection were significantly related to a dimension we call "activation." Eighty 100-day old female Syrian hamsters were placed in circular plexiglas environments in groups of 10. Nineteen days after introduction to the cages, a stress condition was imposed on half the animals (four cages). This consisted of shaking each cage of animals three times a week for three 10-minute intervals. Each group's behavior was videotaped in multiple samples to document pre- and poststress behaviors. Twelve days after the stress condition was initiated, each animal was injected subcutaneously midback with one melanoma tumor fraction. Animals were palpated every three days to determine time to detection of tumor. The videotaped behavior samples were coded for behaviors associated with "activation," inactivity, and interaction. Factor analysis resulted in basically the same first factor of activation found in our previous studies. Hamsters in the nonstressed groups had a significantly longer time to tumor development than those in the stressed groups (22.5 days vs. 12.6 days, p less than 0.005). While no prestress behaviors were associated significantly with time to tumor detection, the poststress activation factor was significantly correlated with longer time to tumor development in the stressed group (r = .61, p less than 0.0001). These results suggest that while the stress condition is more powerful than prestress individual behaviors in affecting the outcome variable, stress appears to interact with the individual behaviors related to "activation" to mitigate the negative effects of stress on tumor growth.
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PMID:Stress-behavior interactions in hamster tumor growth. 347 85

Medium hybrid hens were housed as pairs and observed at three cage heights: 30.0, 42.5 and 55.0 cm, and at three area allowances per bird: 570, 807 and 1045 cm2. With increased height, head stretching, head scratching and body shaking were performed at a higher rate and feeding and cage pecking at a lower rate. There was also an increase in the time spent sitting. With increased area, head scratching, body shaking and feather raising were performed at a higher rate and cage pecking at a lower rate. It is concluded that spatial restriction may increase the cost of performing certain 'comfort' activities, resulting in the reductions in performance rate observed in the above experiments. Welfare implications are briefly discussed and considered to depend on the motivational state of the birds.
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PMID:Effect of cage height and area on the behaviour of hens housed in battery cages. 360 56

During a 28-month period, data were collected on physiological parameters and sociosexual behavior of 13 adult male members of a large mixed-sex group of stumptail macaques living in an outdoor cage. Monthly measurements of plasma testosterone, testis size, and body weight revealed no systematic seasonality. Seasonal variations did occur in branch shaking and grooming (both with low rates in winter), but not in other behaviors studied (copulation, masturbation, aggression). Dominance ranks were stable throughout the study period and were not significantly correlated with mean testosterone levels. Temporal fluctuations in behavioral frequencies did not parallel testosterone fluctuations. Interindividual differences in behavioral frequencies were often correlated with dominance rank, but not with testosterone levels.
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PMID:Testosterone, testis size, seasonality, and behavior in group-living stumptail macaques (Macaca arctoides). 361 55


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