The role of benzodiazepine receptors in the discriminative stimulus properties of delta-9-tetrahydrocannabinol

Twenty male Sprague-Dawley rats were trained to discriminate 3.0 mg/kg delta-9-tetrahydrocannabinol (THC) from its vehicle. Following acquisition of this discrimination animals were tested for generalization to 3.0 mg/kg diazepam. Thirteen animals showed a generalization from THC to diazepam, whereas the remaining seven animals did not. The generalization curve for diazepam was dose-dependent from 0.1 to 10.0 mg/kg in the first group; the latter group showed no generalization from THC at any dose of diazepam in this range. No differences were found between these groups in the generalization curve for THC. The benzodiazepine antagonist Ro 15-1788 (2.0 mg/kg) antagonized the generalization to diazepam in the group that discriminated diazepam as THC. In contrast, Ro 15-1788 increased THC lever responding of 10 mg/kg diazepam in the group which did not generalize from THC. Ro 15-1788 did not alter the discriminability of THC in either group. THC also showed partial generalization to pentobarbital (1 to 10 mg/kg). The generalization was again complete in one subgroup and absent in another, but there was only a 43 percent overlap between the subgroups found with testing for generalization to diazepam. The percent THC lever responding with 3.0 mg/kg pentobarbital was increased by Ro 15-1788 in the group which generalized to diazepam, but not the other group. These data suggest that the discriminative stimulus properties of THC may have some commonality with the effects of diazepam in a subpopulation of rats trained to discriminate THC. These THC-like effects of diazepam are probably mediated by benzodiazepine receptors since they are antagonized by a specific benzodiazepine receptor antagonist.     

Aromatized testosterone attenuates contextual generalization of fear in male rats

Generalization is a common symptom of many anxiety disorders, and females are 60% more likely to suffer from an anxiety disorder than males. We have previously demonstrated that female rats display significantly accelerated rates of contextual fear generalization compared to male rats; a process driven, in part, by activation of ERβ. The current study was designed to determine the impact of estrogens on contextual fear generalization in male rats. For experiment 1, adult male rats were gonadectomized (GDX) and implanted with a capsule containing testosterone proprionate, estradiol, dihydrotestosterone proprionate (DHT), or an empty capsule. Treatment with testosterone or estradiol maintained memory precision when rats were tested in a different (neutral) context 1 day after training. However, male rats treated with DHT or empty capsules displayed significant levels of fear generalization, exhibiting high levels of fear in the neutral context. In Experiment 2, we used acute injections of gonadal hormones at a time known to elicit fear generalization in female rats (e.g. 24 h before testing). Injection treatment followed the same pattern of results seen in Experiment 1. Finally, animals given daily injections of the aromatase inhibitor, Fadrozole, displayed significant fear generalization. These data suggest that testosterone attenuates fear generalization likely through the aromatization testosterone into estradiol as animals treated with the non-aromatizable androgen, DHT, or animals treated with Fadrozole, displayed significant generalized fear. Overall, these results demonstrate a sex-dependent effect of estradiol on the generalization of contextual fear.     

A neuropharmacological analysis of the compensatory-recovery processes in organic failure of the parafascicular complex of the thalamus]

On the model of biological precursors of thinking in animals (cats), in conditions of free behaviour it has been shown that after neurosurgical lesion of various parts of the parafascicular complex restoration is possible of the disturbed functions of generalization and abstraction by neuropharmacological drugs acting on cholinergic, dopaminergic and GABA-ergic systems. Complex interactions are observed between transmitter structures.     

Generalization of conditioned food aversions in grazing sheep and its implications for food categorization

When grazing on heterogeneous pastures, herbivores may rely on food item generalization and categorization processes for reducing information processing while selecting their diet. The objective of this study was to assess the generalization of an aversion by grazing sheep for items differing by one or two criteria from an item against which they were negatively conditioned. Four items cultivated in pots were offered to the animals, resulting from the combination of an intrinsic criterion, i.e. grass species (ryegrass and fescue) and a transitory criterion, i.e. sward height (tall and short). We assessed the generalization process by comparing binary choices between the initially preferred tall ryegrass and the three other items, before and after animals had been partially conditioned against tall ryegrass. This method proved useful in assessing the generalization of an aversion. Sheep did not generalize their aversion on the basis of sward height but rather on species: they increased their preference for tall fescue and decreased their instantaneous preference for short ryegrass after having been conditioned against tall ryegrass. The generalization of an aversion through different states of a same species could indicate the possibility of a species-based categorization by grazing herbivores.     

2 types of chronic epileptogenesis in rabbits during kindling stimulation of the hippocampus

The development of convulsant readiness in rabbits during kindling electrical stimulation of the hippocamp was studied as was the dependence of the motor seizure pattern on the degree of epileptiform activity generalization in the CNS. The kindling electrical stimulation of the hippocamp gave rise to the formation in different rabbits of the two main types of afterdischarges. One of them was characterized by high-frequency and high-amplitude spikes (total duration 8-30 s) and the other one by continuous, rather long (50-100 s) hypersynchronous paroxysms. In the interictal period, the animals with the first type demonstrated the occurrence of spontaneous spikes (in all the brain structures under study) that sometimes progressed to a more or less prolonged seizure discharges. At the same time in the animals with the second type of afterdischarges the EEG in the interictal period was slightly different from normal. Despite this fact the seizures induced by electrical stimulation ran a milder course (short-term clonic seizures) in animals with the first type of afterdischarges as compared to those with the second type (long-term clonicotonic seizures). It is assumed that the severity of the motor seizure does not depend on the degree of epileptic activity generalization in the CNS.     

The use of cycloferon in the therapy of experimental herpetic keratitis]

The cycloferon efficacy was investigated in the treatment of experimental herpesvirus kerato-conjunctivitis in rabbits. The model was demonstrated to reflect the main aspects of herpesvirus eye lesions in humans. Cycloferon application similarly to that of known interferon inducer poludan has been shown to enhance processes of inflammation and subsequent regeneration of eye tissues as well as to decrease mortality of animals due to the generalization of infection.     

Locus of semantic generalization of the galvanic skin response and possible inhibitory influence of conditional stimuli upon unconditional response following conditioning with innocuous and noxious unconditional stimuli

Two different problems were investigated using the GSR index of the orienting reflex (OR): 1) the locus of semantic generalization; and 2) a possible inhibitory influence of the CS upon the UCR. Two experiments were conducted. One experiment employed an innocuous USC, and a second similar experiment used a loud noise as the UCS. Unidirectional word associates were employed in the test of the direction of semantic generalization. Constant and varying CS words were used to test the possible inhibitory influence of the CS upon the UCR. Evidence was obtained of semantic generalization occurring in the training and in the test situation. There was no evidence of the CS developing inhibition over the UCR. Theoretical interpretation of both phenomena were considered. The need for developing theories of conditioning of the OR in humans was emphasized in contrast to current efforts to apply inappropriate cognitive animals learning theories which fail to consider biologic constraints.     

The behavioral effects of the destruction of the nucleus basalis magnocellularis in the cat forebrain]

Behavioural experiments were carried out on cats by the method modelling complicatedly organized non-automatized behaviour with elements of generalization and abstraction. By the results of fulfillment of test tasks by animals with partial destruction of the macrocellular basal nucleus the conclusion is made on the participation of this formation in the structural-functional ensuring of complex integrative forms of activity-thinking and learning. The suggested mechanism of drawing of the basal nucleus in gnostic and cognitive processes in the non-specific ensuring of the system of structures directly participated in thinking and learning.     

Comparative evaluation of methods of inducing Brucella L forms and a study of their adaptibility in the body of animals]

The action of bicillin-3 on Brucella directly in the body of animals enhances their potential ability to convert into L-forms. One of the factors contributing to the generalization of the infection caused by the L-forms of Brucella and to their prolonged persistance in the body is the presence of an L-transforming agent (in this case, bicillin-3), which indicate that the appearing L-forms of Brucella are obviously antibiotic-dependent.     

Enhancing Children's Attitudes About the Humane Treatment of Animals: Generalization to Human-Directed Empathy

Abstract

We assessed the impact of a year-long, school-based humane education program on younger (first and second graders) and older (fourth and fifth graders) children's attitudes toward the treatment of animals. Generalization to human-directed empathy was also measured. Using a pretest-posttest design and ANCOVA, we found that the program enhanced the animal-related attitudes of children differentially, depending on grade level. For younger children, there was no significant difference between experimental (E) and control (C) group attitude means; however, qualitative analysis showed that greater enhancement of attitudes occurred for first grade E group children than for C group children at that grade level. No differences were present on the generalization measure of empathy. For older children, there was a significant difference between E and C group attitude means qualified by grade level—there was greater enhancement of humane attitudes for E group than for C group fourth graders but no difference for fifth graders. On the generalization measure of empathy, posttest means for the E group were significantly greater than means for the C group regardless of grade level. The results contribute to the growing literature on the relation between children and animals and serve to encourage and validate the efforts of humane educators to improve children's caring and kindness toward companion and noncompanion animals.     

The stereospecificity of nicotinamide–adenine dinucleotide-dependent oxidoreductases from plants

1. The stereospecificity of 20 enzymes from plants is reported. 2. The stereospecificity of all known forms of malate dehydrogenase in plants and animals has been shown to be A-specific. 3. The generalization that `the stereospecificity of a particular reaction is independent of the source of the enzyme' is confirmed for a total of 12 plant enzymes. 4. A new generalization is proposed: `When a metabolic sequence involves consecutive nicotinamide–adenine dinucleotide-dependent reactions, the dehydrogenases have the same stereospecificity.'     

Cytogenetic characteristics of the cells of different organs in AKR mice during the development of transplanted lympholeukemia

The process of cell generalization of lymphatic leukemia transplanted clone of AKR mice was studied by the routine and differential methods of metaphase chromosome staining. In 99.5% cases, the cells have an additional small chromosome specific for this type of leukemia, the chromosome being comparable in size with 18-19 pairs of chromosomes of mouse karyotype. Generalization process within 7 days' experiment (from the moment of transplantation up to the moment of animals' death from lymphatic leukemia) appeared to be slower in thymus and bone marrow of AKR mice than in spleen, lymphatic nodes and liver of the same animals with nearly the same generalization rate. A change in the frequency of marked leukemic cells in various organs at different time intervals after transplantation of lymphatic leukemia correlated with intensive cell division of an undulating character in all organs. The data obtained show that hyperdiploid cells carrying the specific additional small chromosome are responsible for the generalization process, this chromosome being also present in spontaneous strain of AKR mice, from which this clone was obtained.     

Generalization mediates sensitivity to complex odor features in the honeybee

Animals use odors as signals for mate, kin, and food recognition, a strategy which appears ubiquitous and successful despite the high intrinsic variability of naturally-occurring odor quantities. Stimulus generalization, or the ability to decide that two objects, though readily distinguishable, are similar enough to afford the same consequence, could help animals adjust to variation in odor signals without losing sensitivity to key inter-stimulus differences. The present study was designed to investigate whether an animal's ability to generalize learned associations to novel odors can be influenced by the nature of the associated outcome. We use a classical conditioning paradigm for studying olfactory learning in honeybees to show that honeybees conditioned on either a fixed- or variable-proportion binary odor mixture generalize learned responses to novel proportions of the same mixture even when inter-odor differences are substantial. We also show that the resulting olfactory generalization gradients depend critically on both the nature of the stimulus-reward paradigm and the intrinsic variability of the conditioned stimulus. The reward dependency we observe must be cognitive rather than perceptual in nature, and we argue that outcome-dependent generalization is necessary for maintaining sensitivity to inter-odor differences in complex olfactory scenes.     

Seasonal dynamics of infecting ability of the flea Citellophilus tesquorum altaicus in the Tuva natural focus of the plague

The infecting ability of the fleas Citellophilus tesquorum altaicus loff, 1936, the main plague vectors in the Tuva natural focus, was experimentally studied in different periods of the epizootic season. Seasonal dynamics in the efficiency of infecting the long-tailed Siberian souslik with the plague causative agent through flea bites was noticed. Seasonal differences in infectivity of the "blocked" flea bites are revealed. An increase of infected experimental animals with a generalization of infection process in the period of epizooty activation in the natural focus was observed. A resistance of the long-tailed Siberian souslik to the plague agent infection through flea bites in the spring season was registered.     

MDA: a psychoactive agent with dual stimulus effects

Rats were trained to discriminate injections of either (+)-amphetamine (1.0 mg/kg) or racemic MDA (1.5 mg/kg) from saline in a two-lever drug discrimination task. After stable discrimination performances (greater than 85%) were attained in each group, stimulus generalization studies were conducted. The amphetamine-stimulus generalized to MDA, but not to the hallucinogenic agent DOM; the MDA-stimulus generalized to both amphetamine and DOM. Taken together with our previous finding that DOM-stimulus generalization occurs to MDA but not to amphetamine, the present study suggests that MDA is capable of producing dual stimulus effects in animals. In addition to these salient features, the results of this study also have an impact on stimulus specificity, and further emphasize the importance of thorough dose-response relationships as related to tests of stimulus generalization.     

Transition rates between specialization and generalization in phytophagous insects

Although most species of animals exhibit specialized patterns of resource use, it is unclear whether specialization evolves at a faster rate than generalization. To test this hypothesis, transition rates toward specialization and toward generalization were estimated using phylogenies from 15 groups of phytophagous insects. Among the groups studied, maximum-likelihood analyses showed that the forward transition rate from generalization to specialization was significantly higher than the reverse transition rate from specialization to generalization (mean ratio of forward to reverse transition rate = 1.47 using uniform branch lengths and 1.76 using Grafen branch lengths). Although phylogenetic conservatism of host-plant use is common, the results suggest that the evolution of specialization is a highly dynamic process. For example, higher transitions rates both toward and away from specialization as well as equal transition rates were inferred. Collectively, the results reveal a tendency for directional evolution toward increased specialization but also indicate that specialization does not always represent an evolutionary dead-end that strongly limits further evolution.     

The prevention of suppurative-septic complications in severe burns by using immunotropic drug preparations in an experiment

The prophylactic and therapeutic action of immunotropic preparations in different doses on the development of Pseudomonas infection of experimental animals with thermal burns was evaluated. Natural marrow and thymic regulatory peptides (myelopid, tactivin and thymalin), as well as the synthetic immunopreparation polyoxydonium, were used for immunocorrection. The study revealed that the injection of these immunomodulators in doses recommended by instructions for use did not affect the course of the infectious process, antibody production by immunocompetent cells and the death rate of experimental animals. The use of the course dose of any of these substances, introduced in a single injection, prevented the generalization of infection. The death rate of experimental animals dropped from 80.3% to 47.2%.     

A century of generalization

We review data from both ethology and psychology about generalization, that is how animals respond to sets of stimuli including familiar and novel stimuli. Our main conclusion is that patterns of generalization are largely independent of systematic group (evidence is available for insects, fish, amphibians, reptiles, birds and mammals, including humans), behavioural context (feeding, drinking, courting, etc.), sensory modality (light, sound, etc.) and of whether reaction to stimuli is learned or genetically inherited. These universalities suggest that generalization originates from general properties of nervous systems, and that evolutionary strategies to cope with novelty and variability in stimulation may be limited. Two major shapes of the generalization gradient can be identified, corresponding to two types of stimulus dimensions. When changes in stimulation involve a rearrangement of a constant amount of stimulation on the sense organs, the generalization gradient peaks close to familiar stimuli, and peak responding is not much higher than responding to familiar stimuli. Contrary to what is often claimed, such gradients are better described by Gaussian curves than by exponentials. When the stimulus dimension involves a variation in the intensity of stimulation, the gradient is often monotonic, and responding to some novel stimuli is considerably stronger than responding to familiar stimuli. Lastly, when several or many familiar stimuli are close to each other predictable biases in responding occur, along all studied dimensions. We do not find differences between biases referred to as peak shift and biases referred to as supernormal stimulation. We conclude by discussing theoretical issues.     

Ontogenetic development of convulsant action of Ro 5-3663 in the rat

Motor seizures were induced by Ro 5-3663 in 156 male albino rats aged 7,12,18,25, and 90 days. Both minimal and maximal seizures could be elicited in 18-day-old and older animals, whereas only maximal seizures were induced in the two youngest groups. ECoG changes were studied in other 21 young rats. First changes induced by Ro 5-3663 were formed by isolated sharp waves in 7- and 12-day-old rats and by episodes of rhythmic activity in older animals. An imperfect form of this rhythmic activity could be seen even in 12-day-old rats. Ictal ECoG activity exhibited an increase in frequency of individual graphoelements, in generalization and in synchronization of activity among different cortical regions with maturation. Correlation between motor and ECoG phenomena was poor in 7-day-old rats and ameliorated with age but it never reached perfection. The actions of Ro 5-3663 are identical with those induced by metrazol but they differ from those elicited by bicuculline or 3-mercaptopropionic acid.     

The effect of unfavorable environmental factors on the mother-fetus system]

The paper provides a generalization of data and the results of own experiments with Wistar rats in the conditions of hypokinesia, immobilization, water deprivation, hypergravity, weightlessness and other factors affecting mother and fetus as a system. It gives a comparison of reactivity of pregnant and non-pregnant animals under stress, and also of the effects of unfavorable impacts sustained during various phases of ontogenesis: in pubertation period, directly before pregnancy and during various phases of pregnancy. It demonstrated that exposition of pregnant animals to unfavorable conditions is accompanied by significant stress of the compensatory-adaptive possibilities of mother aiming to support of homeostasis of the developing fetus. Clear changes develop in fetus only in case the adaptive possibilities of mother turn out inadequate or when the developing organs of fetus become active components of adaptive reaction of mother-fetus system and compensate for functional inadequacy of some mother's organ. The paper discusses the problem of individual features of resistivity and reactivity.