E. V. Filatova

The influence of social conditions on the development of ethanol preference in rats

23 The study of alcoholism as an addictive behavior requires the study of zoosocial relationships. Model experiments with animals showed that dominant rela tionships in communities of alcoholized animals are disturbed [1, 2]. It was found that, when housed in groups, the subdominant animals more readily become ethanol dependent than the dominant ani mals: the former consume more ethanol and earlier become alcohol addicts [1]. In addition, an increase in the physical aggression as a result of alcoholization was demonstrated [3, 4]. It was assumed that ethanol, in general, stimulates social activity [5]. It is known that, in animal colonies, alcohol dependence develops at different rates in different animals depending on their social status [6]. In isolation, conversely, alcohol preference is observed in the dominant animals [7, 8]. The question as to how group or individual ethanol consumption under conditions of group housing affects the development of alcohol addiction in ani mals remains to be answered. The goal of this work was to study the pattern of development of alcohol depen dence during individual alcohol consumption in ani mals housed in the groups where other members were not alcoholized in comparison to the development of alcohol dependence in the groups of animals where all members were alcoholized. Experiments were performed with 48 male Wistar rats weighing 250–300 g. To increase the intensity of aggressive interactions, adult males were isolated from the other animals for two weeks. The separated ani mals were kept in individual metal cages (200 × 150 mm) and received water and food ad libitum. After 14 days of isolation, rats were placed in cages 570 × 350 mm; (three animals in each cage) with fresh litter. To determine the hierarchical relationships between the rats, the interactions between them were observed for the first 15 min after placing them into one cage. To analyze the social interactions, four parameters were determined: the number of attacks, the number of defensive and submissive postures, and interactions expressed in grooming and sniffing of partner’s body. Then, the rats were housed in this cage in the same composition. After three days of housing in groups, the interactions between animals were studied again using the resident–intruder test: a foreign male was placed into the cage and the social behavior of rats was recorded for the first 15 min. Then, at the 15th minute, a female was placed into the cage and the behavior of rats, including the copulative acts, was recorded. On the basis of the interactions between animals recorded in all tests, the rank of animals (dominant, subdomi nant, and subordinate) was determined. Studies were performed in experimental groups of three types. In one type of groups, only one rat of each group was given alcohol, whereas the other members received water. Such individual alcoholization was studied in animals of different hierarchical levels. In the second type of groups, alcohol solution was given to all animals living together. In the third type of groups (control), all rats received water. In the constant housing cages, waterers were absent. For drinking, each rat was placed daily for 1 h in an individual cage, where it had access to liquid. In our experiments, we used the forced alcoholization model. For two months, all the rats subjected to alco holization had no access to any liquid except for 10% ethanol. All other rats received water. The level of alcohol preference was assessed in the “two bottle test.” A rat was placed in an individual cage with two waterers, one of which was filled with water and the other one contained 10% alcohol. The volume of liq uid consumed from each waterer determined and the number of approaches to each waterer were counted for 15 min. During the experiment, this test was per formed three times—before as well as 27 and 54 days after the beginning of forced alcoholization. The dynamics of different parameters was moni tored in the “Suok test” [9]. In this test, a rat was placed on a 5 cm wide rod, which was divided into PHYSIOLOGY

Social Interactions Affect the Ethanol Preference Forming in Rats

Model experiments with animals have showed that social relationships in communities of alcoholized animals are disturbed. The goal of this work was to study patterns of alcohol dependence development during individual alcohol consumption in animals housed in the groups where other members were not alcoholized in comparison to the groups of animals where all members were alcoholized. After 14 days of isolation 48 male Wistar rats were placed by 3 into standard cages. Hierarchical relationships between the rats were observed for the first 15 min after placing them into one cage. After three days of housing in groups the interactions between animals were studied again using the resident–intruder test. On the basis of the interactions recorded in all tests, the animal rank was determined. Studies were carried out in experimental groups of three types: 1) only one rat of each group was given 10% ethanol, whereas the other members received water. Such individual alcoholization was studied in animals of different hierarchical levels. 2) 10% ethanol was given to all animals living together. 3) all rats received water – control group. The level of alcohol preference was assessed in the “«two bottle» test” before and after 27 and 54 days of experiment. It was found, that social interactions significantly affect the development of ethanol preference in rats. Initial high anxiety level as well as subordinate and subordinate ranks predispose to ethanol intake. In groups of drinking together rats ethanol preference develops significantly higher than in case of drinking alone rat housed with alcohol free cage mates. Housing of drinking alone rat with alcohol free rats induces the aversive reaction to ethanol instead of their rank status.

The Relationship between Prefrontal Cortex Neuron Activity in the Two Hemispheres on Performance of a Choice Task in a Two-Ring Maze

Neuron activity in two symmetrical areas of the prefrontal cortex in the left and right hemispheres of the rat brain (55 and 47 neurons, respectively) was recorded as the animals performed a behavioral choice task in a two-ring maze. Experiments were performed in two sets of conditions – i) working with a conditioned signal, when excursions to the side indicated by the signal were reinforced, and ii) without a signal, when any excursion was reinforced. The levels of involvement of a neuron in different steps of the behavioral program were evaluated in terms of the level of differential activity, i.e., differences in neuron activity in right- and left-sided performances. In conditions in which the animal took the decision without orienting itself to external signals (in two behavioral situations: working without signals and erroneous performance of the program), there was a predominance of differential activity in the left hemisphere. In correct performances of the program, activity dominated in the right hemisphere. This appears to be evidence of a consistent dynamic in the interaction between the hemispheres depending on external and internal conditions and the special role of the right hemisphere in learning mechanisms and inclusion of the external determinant in the adaptive response system.

Long-Term Ethanol Alcoholization Decreases Levodopa- Induced Aggressive Behavior in Rats

One of the old but still unsolved problems in psychiatry is the treatment of patients with a dual diagnosis of schizophrenia and alcoholism. Numerous clinical studies failed to explain unambiguously the mechanisms of formation of these comorbid disorders. Experimental modeling of dual disorders was carried out using a model of schizophrenia based on the impaired development and dopamine hypothesis of schizophrenia. To model comorbid experimental schizophrenia and alcohol abuse, the dopamine precursors, Levodopa/Carbidopa (LC), were used in combination with 15% ethanol. The aim of this study was to investigate social behavior of rats receiving LC and exposed to intermittent semi-compulsory alcoholization. After three months of the experiment, there were significantly more interactions (including aggressive–attacks, fights, bites) and submissive postures in the group of rats that received LC. Combined LC/ethanol administration did not alter rat social behavior in contrast to ethanol administered alone.

Sucrose-enriched diet during maturation increases ethanol preference in rats

In the present study we used a diet enriched with 10% sucrose, which was consumed by adolescent animals of the experimental group for one month. We found that consumption of sweet food during sexual maturation affected alcohol preference, anxiety, and locomotor and exploratory activity in the adult rats. Our data show that easily available tasty food during adolescence probably impairs the reward system and serves as a trigger of future alcohol preference.

A Two-Ring Maze for Studies of the Behavior of Laboratory Animals

The behavior of rats was studied in a two-ring maze in which the animal could make its own choice of one of two trajectories of the same length, independently returning to the start point. All maze sectors – starting chamber, signal sector, arm, and feeding sector – were separated by one-way doors. The time structure of passage through the maze sectors reflected both the level of the animal’s motivation and fully defined aspects of behavior, i.e., attention, short-term memory, and long-term memory, as well as the cognitive aspect, i.e., taking movement trajectory decisions on the basis of the conditioned signal presented, and the emotional aspect, i.e., assessment of the result of the action. Analysis of the time parameters of the activity allowed changes in various behavioral components to be evaluated in relation to treatment applied to the animals and ongoing status. We suggest that this behavioral model will be useful in different types of neuropharmacological, electrophysiological, and behavioral experiments.

Pharmacological action of phenazepam and caffeine on emotional sphere changes ethanol preference in Wistar male rats

Earlier we showed that direction of changes in the initial anxiety level during compulsory alcoholization was more essential for development of alcohol preference than the initial anxiety level per se. The goal of this work was to study effect of the anxiety level changes on development of ethanol preference in Wistar male rats pharmacologically affected by phenazepam and caffeine. Out of four groups (60 rats) over the period of 4 months, group I had access to 10% ethanol, group II-to 10% ethanol with 0.4 g/l caffeine, group III-to 10% ethanol with 0.5 mg/l phenazepam, and group IV (control)—to water only. The anxiety level and behavioral parameters were evaluated before the onset of the experiment and every 5 weeks thereafter by using the open field test. The ethanol preference was determined by the 2-glass test before the onset of the experiment and every 4 weeks thereafter. In the experimental groups, the long-term consumption of ethanol, ethanol with caffeine, and ethanol with phenazepam led to an increase in alcohol preference as compared with control. A decrease in motor activity under compulsory alcoholization was found to correlate positively with the low level of alcohol preference. Rats that consumed ethanol with caffeine sensitive to this anxiety-enhancing psychostimulant developed ethanol preference faster. The rats insensitive to caffeine developed no alcohol preference. The rats sensitive to the sedative effect of phenazepam were less anxious and did not prefer alcohol subsequently. In rats insensitive to phenazepam, anxiety increased and alcohol preference developed.

Modeling of schizophrenia with Levodopa+Carbidopa

Experimental modeling of mental disorders on animal helps both to reveal mechanisms of the appearance of pathology and to direct the ways of effective methods of its treatment. The goal of the present work was to create a new model of schizophrenia by oral Levodopa+Carbidopa (LC) administration. Introduction of LC to rats was found to induces a significant decrease of emotional reactions, hypersensitivity to sound stimuli, a reduction of exploratory activity, stereotype behavior, and motor hyperactivity in occasional rats. It is concluded that the LC administration to rats may be used as an alternative dopaminergic model of schizophrenia on animals.

The amount and composition of monkey parietal cortex neurons that are active during functionally different behaviors.

117 The correlation of impulse activity of parietal corr tex neurons with various behavioral activities has been studied in considerable detail. The activity of parietal cortex neurons during the preparation to certain movements and control of them with and without an assistance of vision has been described [5, 6]. There is evidence for the participation of the parietal cortex in processes of sensory integration, memory, and learnn ing [7, 12]. This indicates a great variety of possible impacts of parietal cortex neurons on establishment of functionally different behavioral actions. At the same time, comparison of the results obtained by different authors is complicated because of the dependence of observed neuronal reactions on behavioral context and different conditions of their recording [8]. Therefore, investigation of a range of impacts of neuronal activity on behavior, apparently, is not enough for understandd ing the mechanisms underlying brain activity. The aim of this work is acquisition of comparable data about differences in impulse activity of parietal cortex neurons generated in connection to implementation of functionally heterogeneous behavioral actions. The experiments were carried out on a monkey (Macaca nemestrina), which was trained to perform a multistage test program [2]. The monkey remained in a primatological armchair, the head and hand move ments being not restricted. The program of the test included 15 stages [4]. The experimental program started with a warning signal. Then, 1600 ms after terr mination of the warning signal (1000 Hz), which lasted for 400 ms, the monkey obtained admittance to levers of an experimental installation, moved its hands toward them, pressed, and held them for 300 ms until the conditioned signal (stages 1–6). Lighttemitting diodes, switched on to the right or the left from the monkey in the random order, were used as the condii tioned signal. Response to the conditioned signal (7), decisionnmaking time of choice of the working hand (8), and the initial and final stages of movement of this hand (the other hand was holding another lever) towards the switch of the trough (9, 10) have been singled out. The subsequent stages of the program were the switching on of the trough with fingers of the chosen hand (11), response to a click of the trough (12), and waiting for a food pill (13). At stages 14–15, each lasting for 500 ms, the monkey returned to the initial position and could use both hands again; it grabbed the …

Effect of individual peculiarities of emotional sphere on formation of preference of ethanol in female and male Wistar rats

Individual characteristics of animal behavior can serve a prognostic parameter of predisposition to use of alcohol. The goal of the work was to study dynamics of formation of preference of alcohol at early stages in the process of forced alcoholization in male and female rats as well as the accompanying changes in behavior parameters. For 3 months, the rats were submitted to the forced alcoholization with 10% ethanol. Each week the rats were tested in the “two-glass trial.” Individual peculiarities of all animals were evaluated prior to, after 6 weeks, and after the end of the experiment with aid of the “open field test” and “Suok-test.” Results showed that the male rats demonstrating by the end of the experiment the significantly higher level of the alcohol preference, demonstrated at the initial stages of the forced alcoholization the significantly lower preference as compared with the remaining ones. These rats also showed before alcoholization the lower levels of the motor and exploratory activities as compared with control. On the contrary, the individuals that by the end of the experiment did not differ from control by the level of the alcohol preference demonstrated prior to alcoholization in the “Suok-test” the higher anxiety level. In females there was observed a positive correlation of a decrease of the anxiety level in the process of alcoholization with a rise of ethanol consumption. Thus, in male rats, the prognostic parameter predicting formation of the abuse can serve the degree of alcohol preference at the initial stages.