The behavior of the homozygous and heterozygous sub-types of rats which are genetically-selected for diabetes insipidus: a comparison with Long Evans and Wistar stocks

Several aspects of spontaneous and conditioned behavior (food and water intake, locomotion and emotionality, passive and active avoidance acquisition and retention) of standard (albino and pigmented) rats, and rats heterozygous (HEDI) and homozygous (HODI) for diabetes insipidus, are reviewed. As would be expected, HODI rats have been repeatedly found to consume far more fluid than either HEDI or control rats. Pigmented rats appear to be more active than albinos. HODI rats exhibit less marked emotional responses than do control rats, among which the pigmented ones exhibit the highest emotionality. Light aversion is more evident in albino than in pigmented rats. No differences are found among HEDI, HODI and normal Long Evans rats. It is quite difficult to provide a clear-cut statement concerning inter-strain differences in passive avoidance behavior, possibly because of the variety of techniques employed. In any case, HODI rats do not perform worse than normal controls do. In one-way active avoidance paradigms, pigmented rats perform better than albinos, and the performance of HODI rats does not differ from that of controls. In two-way avoidance paradigms, albinos appear to outperform pigmented rats. Once again, there are no obvious differences between HODI and control animals. In addition to indicating that HODI rats may actually be less emotional than the other groups of rats reviewed here, the studies described once again fail to confirm the previously alleged functions of vasopressin in memory consolidation.     

3H-Diazepam binding sites in Roman high- and low-avoidance rats

The binding of 3H-diazepam to membrane benzodiazepine receptors was examined in 2 psychogenetically selected lines of rats, which differ according to the selection criterion in avoidance behaviour (RHA/Verh greater than RLA/Verh) and, in addition, in emotionality (RHA/Verh less than RLA/Verh). RHA/Verh rats tended to show higher specific diazepam binding in all CNS-subregions when compared with RLA/Verh animals. Significant differences were found in the cortex, striatum, hippocampus, thalamic region and pons-medulla. These results reinforce the contention that a system involving benzodiazepine receptors may play a role in emotional behaviour.     

Comparison of the ototoxic effect of kanamycin on albino and pigmented rats, studied using an operant method.

A study was made of the effect of daily administration of kanamycin (400 mg kg-1) on the hearing of Wistar albino and Lister hooded (pigmented) rats, which had been conditioned to discriminate an acoustic signal. In all animals except one, the drug caused severe, permanent hearing impairment and there was no difference between albino and pigmented rats in onset or degree. Other work has suggested a mediatory role for melanin pigment in such drug ototoxicity but the significance of this must be questioned in view of the failure to find any differences in functional deficit.     

Comparison of the ototoxic effect of kanamycin on albino and pigmented rats,studied using an operant method

Summary A study was made of the effect of daily administration of kanamycin (400 mg kg^–1) on the hearing of Wistar albino and Lister hooded (pigmented) rats, which had been conditioned to discriminate an acoustic signal. In all animals except one, the drug caused severe, permanent hearing impairment and there was no difference between albino and pigmented rats in onset or degree. Other work has suggested a mediatory role for melanin pigment in such drug ototoxicity but the significance of this must be questioned in view of the failure to find any differences in functional deficit.This work was supported by a Fellowship toE. S. Harpur from the Department of Health and Social Services (Northern Ireland).     

Heritable variation for aggression as a reflection of individual coping strategies

Evidence is presented in rodents, that individual differences in aggression reflect heritable, fundamentally different, but equally valuable alternative strategies to cope with environmental demands. Generally, aggressive individuals show an active response to aversive situations. In a social setting, they react with flight or escape when defeated; in non-social situations, they react with active avoidance of controllable shocks and with sustained activity during an uncontrollable task. In contrast, non-aggressive individuals generally adopt a passive strategy. In social and non-social aversive situations, they react with immobility and withdrawal. A main aspect of these two alternative strategies is that individuals with an active strategy easily develop routines (intrinsically determined behaviour), and consequently do not react (properly) to 'minor' changes in their environment, whereas in passively reacting animals it is just the other way around (extrinsically determined behaviour). It has become clear that active and passive behavioural strategies represent two different, but equivalent, coping styles. The coping style of the aggressive males is aimed at the removal of themselves from the source of stress or at removal of the stress source itself (i.e. active manipulation). Non-aggressive individuals seem to aim at the reduction of the emotional impact of the stress (i.e. passive confrontation). The success of both coping styles depends upon the variability or stability of the environment. The fact that aggressive males develop routines may contribute to a fast execution of their anticipatory responses, which is necessary for an effective manipulation of events. However, this is only of advantage in predictable (stable) situations, but is maladaptive (e.g. expressed by the development of stress pathologies) when the animal is confronted with the unexpected (variable situations). The flexible behaviour of non-aggressive individuals, depending strongly upon external stimuli, will be of advantage under changing conditions. Studies on wild house mice living under natural conditions show how active and passive coping functions in nature, and how the two types have been brought about by natural selection.     

Genetic and environmental influences on behavioral and neurochemical aspects of emotionality in rats

Summary Three pairings of rats (two derived from divergent, selective breeding and one from divergent environmental conditions) were compared with regard to behavioral and hormonal parameters. Striking differences were observed: results obtained in our own laboratory as well as those found in a review of the literature pointed to higher emotionality (e.g., increased defecation and corticosterone secretion, etc.) in Roman low-avoidance, Wistar-Kyoto and group-housed rats, as compared to their respective counterparts, Roman high-avoidance, spontaneously hypertensive, and individually housed Wistar rats. Concomitant receptor binding studies reviewed here (³H-diazepam- and³H-imipramine-binding sites) have revelaed, however, less consistent intrapair differences.     

Heritable variation for aggression as a reflection of individual coping strategies

Evidence is presented in rodents, that individual differences in aggression reflect heritable, fundamentally different, but equally valuablealternative strategies to cope with environmental demands. Generally, aggressive individuals show an active response to aversive situations. In a social setting, they react with flight or escape when defeated; in non-social situations, they react with active avoidance of controllable shocks and with sustained activity during an uncontrollable task. In contrast, non-aggressive individuals generally adopt a passive strategy. In social and non-social aversive situations, they react with immobility and withdrawal.A main aspect of these two alternative strategies is that individuals with an active strategy easily develop routines (intrinsically determined behaviour), and consequently do not react (properly) to minor changes in their environment, whereas in passively reacting animals it is just the other way around (extrinsically determined behaviour). It has become clear that active and passive behavioural strategies represent two different, but equivalent, coping styles. The coping style of the aggressive males is aimed at the removal of themselves from the source of stress or at removal of the stress source itself (i. e. active manipulation). Non-aggressive individuals seem to aim at the reduction of the emotional impact of the stress (i.e. passive confrontation). The success of both coping styles depends upon the variability or stability of the environment. The fact that aggressive males develop routines may contribute to a fast excution of their anticipatory responses, which is necessary for an effective manipulation of events. However, this is only of advantage in predictable (stable) situations, but is maladaptive (e.g. expressed by the development of stress pathologies) when the animal is confronted with the unexpected (variable situations). The flexible behaviour of non-aggressive individuals, depending strongly upon external stimuli, will be of advantage under changing conditions.Studies on wild house mice living under natural conditions show how active and passive coping functions in nature, and how the two types have been brought about by natural selection.     

Genetic and environmental influences on reactive and spontaneous locomotor activities in rats

Paired groups of rats (derived from divergent, selective breeding or living in divergent environmental conditions) were compared with regard to locomotor activities. Intrapair differences were found to vary non-systematically, depending upon whether the rats were initially exposed to a test-environment with or without a slight environmental modification (reactive activities), or were allowed to habituate extensively to the environment (spontaneous activity). Since the behavioral patterns were found to represent distinct entities, this pointed to the necessity of differentiating clearly between spontaneous and reactive activities and indicated, once again, that both genetic and environmental influences are important in these behaviors and must be taken into account. Accepting and controlling for these variables makes it possible to use the factor of individual differences in laboratory animal behavior to advantage.     

3H-Diazepam binding sites in roman high- and low-avoidance rats

Summary The binding of³H-diazepam to membrane benzodiazepine receptors was examined in 2 psychogenetically selected lines of rats, which differ according to the selection criterion in avoidance behaviour (RHA/Verh>RLA/Verh) and, in addition, in emotionality (RHA/Verh相似文献   

Genetic determinants of individual differences in avoidance learning: Behavioral and endocrine characteristics

Bidirectional genetic selection for good and poor active avoidance learning in a shuttle box has been carried out in three independent laboratories using remarkably similar discrete-trial training procedures. The resulting strains are known as the Roman High and Low Avoidance (RHA and RLA), the Syracuse High and Low Avoidance (SHA and SLA) and the Australian High and Low Avoidance (AHA and ALA) strains, respectively. An additional unidirectionally selected strain, known as the Tokai High Avoider (THA) strain was developed in Japan using a free-operant Sidman avoidance procedure in a Skinner box. This paper reviews the selection of the Syracuse strains, enumerates the various behavioral and endocrine characteristics of the strains, and compares them to the other similarly selected strains. The behavioral work suggests that genetic selection from diverse breeding stocks has resulted in common characteristics that differentiate the strains in the emotional, not learning, domain. The endocrine data, however, are somewhat at odds. The Syracuse strains differentiate one way with respect to endocrine function, and the Roman strains differentiate in the opposite way. We suggest, therefore, that the endocrine correlates are not tightly linked to the avoidance genotype. Genetic analysis of all of the selected strains for both the avoidance phenotype and the endocrine correlates will be needed to test this hypothesis.Preparation of this paper was supported by research grant MH-39230-3 from the National Institute of Mental Health.     

The influence of pigmentation of rats and guinea-pigs on the ototoxicity of kanamycin and neomycin.

Following the finding that melanin pigment played a role in the accumulation of ototoxic drugs in the inner ear, an investigation was made of the possible influence of the pigmentation of animals on their susceptibility to the ototoxic effects of drugs. Hearing acuity was assessed by measurement of acoustic startle reaction. Preliminary experiments suggested that pigmented animals might be more likely to suffer hearing impairment following ototoxic drug administration. However, in a controlled study using rats treated with kanamycin, it was not possible to confirm this and albino animals appeared no less vulnerable than pigmented animals to kanamycin-induced deafness.     

Genetic and environmental influences on behavioral and neurochemical aspects of emotionality in rats

Three pairings of rats (two derived from divergent, selective breeding and one from divergent environmental conditions) were compared with regard to behavioral and hormonal parameters. Striking differences were observed: results obtained in our own laboratory as well as those found in a review of the literature pointed to higher emotionality (e.g., increased defecation and corticosterone secretion, etc.) in Roman low-avoidance, Wistar-Kyoto and group-housed rats, as compared to their respective counterparts, Roman high-avoidance, spontaneously hypertensive, and individually housed Wistar rats. Concomitant receptor binding studies reviewed here (3H-diazepam- and 3H-imipramine-binding sites) have revealed, however, less consistent intrapair differences.     

Interaction of salicylate and noise results in mortality of rats

Summary Survival as a function of salicylate dose and the intensity of environmental noise was investigated in 150 adult female pigmented rats. Rats were assigned to groups (n=6/group) defined by combinations of salicylate levels from 0- (saline) to 300 mg/kg, injected subcutaneously, and noise levels from ambient noise to 98 dB SPL, presented daily for 10-h periods for up to 17 days. Mortality occurred in groups exposed to the higher combinations of salicylate and noise.     

Influence of substance P and fragments on passive avoidance behavior

Summary N-terminal and C-terminal fragments of substance P (SP) have been shown to exert opposite effects on antinociception, grooming and fighting in mice. The present experiments explored whether these findings could be generalized to passive avoidance behavior. Substance P (SP-(1-11)) and the c-terminal, fragment pyroglutamyl-SP-(7-11) attenuated passive avoidance behavior when picogram amounts were injected into the nucleus accumbens. In contrast, the N-terminal fragment, SP-(1-7) had an opposite effect and facilitated passive avoidance behavior.     

Influence of substance P and fragments on passive avoidance behavior

N-terminal and C-terminal fragments of substance P (SP) have been shown to exert opposite effects on antinociception, grooming and fighting in mice. The present experiments explored whether these findings could be generalized to passive avoidance behavior. Substance P (SP-(1-11] and the C-terminal fragment pyroglutamyl-SP-(7-11) attenuated passive avoidance behavior when picogram amounts were injected into the nucleus accumbens. In contrast, the N-terminal fragment SP-(1-7) had an opposite effect and facilitated passive avoidance behavior.     

Alleviation of mortality induced by salicylate and stress

Protection from the deleterious effects of the interaction of environmental stress and salicylate by calcium supplement was investigated in 96 pigmented rats. Within a 2×2×4 factorial design, rats were assigned to groups defined by:A) ad lib access to 1) plain tap water, or 2) 50 mM calcium chloride solution;B) exposure to stressors consisting of daily 10 h periods of 1) 98 dB SPL noise, or 2) confinement precluding movements;C) daily injections of 233, 350, or 410 mg/kg of sodium salicylate or the saline vehicle. For subjects maintained on tap water, weight loss and mortality increased with salicylate levels, with all subjects dying in the group drinking water and injected with 410 mg/kg. Calcium protected all of the subjects in the noise stress group but not in the confined group.     

Genetic and pharmacological models of cholinergic supersensitivity and affective disorders

Summary Increased muscarinic sensitivity has been associated with altered hormonal states (hypothyroidism and hyperadrenocorticism), chronic administration of muscarinic antagonists or antidepressants with muscarinic actions, selective breeding for anticholinesterase sensitivity, and certain inbred strains of rats and mice. Thus, both genetic and environmental factors may influence muscarinic receptor sensitivity. The reasonably detailed studies on the selectively-bred rats have revealed that the Flinders Sensitive Line (FSL) rats weigh less, are less active, are more sensitive to muscarinic agonists and to stressors, and have higher concentrations of hippocampal and striatal muscarinic receptors than normal, or the selectively-bred, Flinders Resistant Line (FRL) rats. Thus, there are a number of parallels between FSL rats and depressed humans. The FSL rats may be the first animal model of depression to mimic the actual trait of depression, and not just the state.     

Stress and putative endogenous ligands for benzodiazepine receptors: The importance of characteristics of the aversive situation and of differential emotionality in experimental animals

The relationships between anxiety/stress, possible endogenous ligands for benzodiazepine receptors and the behavioral modification by drugs are discussed in this short review, including the specific characteristics of elements involved in those interactions, e.g. ones concerning the aversiveness of the stressful situation and the nature of the organism under investigation. These are important factors when considering aversive tasks, insofar as they may involve stressful conditions which differ in intensity and in the degree of control afforded the subject. These characteristics may well lead to differing functional effects on GABA-gated chloride channels or, in other words, to an incongruous balance between endogenous benzodiazepine receptor agonist and inverse agonist activity. This is not surprising, as it is well known that different forms of stressors often actually produce divergent behavioral, physiological and biochemical effects. This review also illustrates the necessity of taking into account the variable effects of stressors and/or drugs on animals differing in reactivity or emotionality, even in the case of non-selected stocks. The implication is made that, by genetic and/or environmental manipulation of the emotional state of the animals used, it will be possible to obtain more clearly definable results in neuropharmacological and psychopharmacological studies.     

The AA and ANA rat lines,selected for differences in voluntary alcohol consumption

Summary The offspring of rats that voluntarily select larger quantities of alcohol are heavier consumers of alcohol than the offspring of rats that tend to avoid it. Such selective breeding, repeated over many generations, was used to develop the AA (Alko, Alcohol) line of rats which prefer 10% alcohol to water, and the ANA (Alko, Non-Alcohol) line of rats which choose water to the virtual exclusion of alcohol. In addition to demonstrating the likely role of genetic factors in alcohol consumption, these lines have been used to find behavioral, metabolic, and neurochemical correlates of differential alcohol intake. Some of the line differences that have been found involve the reinforcing effects of ethanol, the changes in consumption produced by alcohol deprivation and nutritional factors, the behavioral and adrenal monoamine reactions to mild stress, the development of tolerance, the accumulation of acetaldehyde during ethanol metabolism, and the brain levels of serotonin. It is hoped that these studies will lead to a better understanding of the genetically-determined mechanisms that influence the selection of alcohol.     

Effects of brain monoamine depletion on thermoregulation, active avoidance, and food and water intake in rats

Intraventricular administration of 6-OHDA or 5,6-DHT suppressed food intake, whereas their effect on active avoidance produced a suppression with the former and an enhancement with the latter. The increased water intake was specifically associated with 5,6-DHT treatment in rats.