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DBA/2, CBA mice, and their F1 hybrids (first series) and 101/HY and C3H mice (second series) were injected as neonates (2-7 days of life) with Semax (sc., 7 microg per animal). Semax is a peptide analogue of ACHT4-10 fragment which is resistant to degradation. The common feature of remote effects of both Semax and saline injections was the set of changes in the open-field behavior in adult (2.5- to 3-month-old) animals as compared to intact mice. Unexpectedly, the neonatal saline injections induced many changes in adult behavior, part of these effects being genotype-dependent. The most conspicuous shifts (genotype-dependent increase or decline) in freezing, grooming and rearing scores were displayed by DBA/2 and C3H mice, whereas the hole-poke frequencies were significantly changed in CBA and C3H mice. Squares crossed in the center of arena and rearing number were significantly increased in saline group of DBA/2 mice, whereas in Semax-injected DBA/2 group they were approximately equal to the level of intact mice. This means that the remote effects of noxious stimulation (injections of saline) were in some ways "compensated" as the result of concomitant peptide effect. At the same time, the numbers of freezing and grooming episodes were also increased in these groups. Because exploratory behavior and manifestations of anxiety increased or decreased simultaneously, it proves to be difficult to ascribe these changes to behavioral modulation along the "novelty seeking--anxiety" axis. In mice of other genotypes, changes in the same indices of the open-field behavior were revealed, but these changes were different in their direction. It was suggested that the complex patterns of postnatal behavior was the result of neonatal injections modulating subsequent brain development.

The levels of dopamine (DA) was determined by intracerebral microdialysis in vivo in KM rats selected for high audiogenic epilepsy, and in Wistar rats selected for nonsusceptibility to loud sound. The basal level of dopamine was 25% higher in the KM rats (P < 0.05). A single amphetamine injection (1 mg/kg body weight, intraperitoneously) caused a significant increase in the DA basal level up to 250-260% in animals of both genotypes. However, in Wistar rats, the level of DA reached maximum as soon as 20 min after amphetamine administration, whereas in KM rats, this happened only after 120 min. After a single injection of the antagonist of D2 and D3 dopamine receptors raclopride (1.2 mg/kg of body weight, intraperitoneously), an increase in the level of DA was similar in amplitude in rats of both genotypes (up to about 210%); however, this occurred 20-30 and 100 min after raclopride administration to Wistar and KM rats, respectively. This evidence suggests that the genetic defect of KM rats, namely, the high level of audiogenic epilepsy, is caused by abnormalities of the neuromediator brain systems and presumably accompanied by the regulatory gene dysfunction.

We studied the effect of neonatal treatment with pharmacological preparations (Semax and buspiron) and solvents (distilled water and physiological saline) on the pain threshold in 3-4-month-old mice of 6 genotypes. Neonatal administration of the solvent (nociceptive stimulation) decreased pain thresholds in DBA/2, 101/HY, and RSB males, but not in female mice and animals of other strains. Neonatal administration of Semax significantly increased pain thresholds in adult DBA/2 and 101/HY males compared to those in animals neonatally treated with the solvent. Injection of buspiron in the neonatal period decreased pain thresholds in RLB males.

Principal component analysis of behavioural measures together with body and brain weight of hybrid F2 mice crosses between two lines selected for large (LB) and small (SB) brain weight yielded eight-factor solution explaining 75.1% of total variance. Two of eight factors had sufficient loading on brain weight and several behavioural measures. The factor analysis showed that, among F2 hybrids, mice with larger brain weight were characterised, in open-field test, by higher scores of locomotion in the periphery of arena and of rearing, as well as less frequent grooming and freezing than mice with smaller brain weight. F2 hybrids with larger brain weight moved faster and displayed stereotyped behaviour in the cross-maze test more frequently. In general, this diversity is in accord with the behaviour differences between parent LB and SB lines. The results show that, in mice fear-anxiety and stereotypic behaviours, which are known to interfere with normal exploration and learning of the environment, are causally connected with brain weight.

The remote effects of neonatal (on the 3d-to-9th postnatal days) ketamine injections (10 and 50 mg/kg in 20 microliters of distilled water, s.c.) were analyzed in adult Wistar, WAG/Rij, and KM (a strain with high audiogenic sensitivity) rats. Both ketamine and water injections increased pain sensitivity in adult rats. Neonatally injected water increased the mean score of seizures in Wistar and WAG/Rij, whereas ketamine water solution injected in the dose of 50 mg/kg did not change the seizure intensity (as compared to the intact control). Consequently, ketamine significantly reduced the mean score of the audiogenic seizure fit without change in its latency. In highly sensitive KM rats the neonatally injected ketamine (50 mg/kg) significantly shortened the mean latency of the fit onset, and fit stages developed faster. Thus, the neonatal ketamine injection increased the audiogenic seizure susceptibility of brain structures in KM rats.

Variations in the extent of adult neurogenesis and natural and experimental factors controlling it have been described in laboratory animals. The wide range of variation seen even within a species, the mouse, raises the question as to which rates of neurogenesis can be expected in natural populations. Answering this question is important to evaluate the functional significance of adult neurogenesis under natural conditions and to define the factors controlling it. To address this issue, we investigated four species of wild-living rodents and outbred laboratory mice using markers for proliferating cells, Ki-67, and developing neurons, doublecortin and NeuroD. We found about four times as many Ki-67-positive cells per mm3 granule cell layer in two wood mouse species (Muridae; Apodemus spp.) than in bank and pine voles (Arvicolidae; Clethrionomys glareolus and Microtus subterraneus). Laboratory mice show proliferation rates between wood mice and voles. Markers for developing neurons, NeuroD and doublecortin, reflect the findings of proliferation activity. Hippocampal cell proliferation decreases dramatically with age in wild-living species. The onset of the downregulation varies among species. It occurs late in the life span of the yellow-necked wood mouse. In aged animals, the number of proliferating cells per mm3 granule cell layer is reduced to 19% of the adult value. Downregulation occurs early in pine voles, in which cell proliferation in adult animals is reduced to 33% of juvenile values. Proliferation and age-dependent changes along the deep border of the alveus and angular bundle follow those of the dentate gyrus. We conclude that cell proliferation and neurogenesis in the dentate gyrus vary significantly among wild-living rodents, and that they are downregulated with age, but at species-specific time points., (2004 Wiley-Liss, Inc.)

In adult Wistar, KM, and Wag/Rij rats, the threshold of pain sensitivity (tail-flick test) and degree of spasm attack in response to a strong sound were estimated after neonatal administration of Semaks (analog of ACTG4-10 fragment) or after placebo (administration of saline for the control of the effect of neonatal pain stimulation). These neonatal influences did no affect the rates of sensorimotor maturation at an early age (Fox tests), i.e., did not affect directly the physiological activity of rat pups at the age of up to 21 days. In all control rats injected with saline (pain stimulation), the latent periods of audiogenic attacks increased reliably, while their degree decreased. Administration of Semaks "raised" these parameters to the lvl of those in intact animals, i.e., increased the sensitivity to sound. Neonatal administration (per os) of caffeine to KM rats increased reliably the latent period of audiogenic attacks. The thresholds of pain sensitivity in the rats of all strains were significantly lower than in the intact control, just as the level of dopamine in the hippocampus of KM rats. These data are interpreted as an evidence of changes in the development of some brain systems in response to neonatal influences.

The effects of ethanol injections on the F2 offspring of the cross between large-brain (LB) and small-brain (SB) mouse strains selected for high and low relative brain weights, respectively, have been studied. The parental strains have significantly differed in brain weight for many generations. The effects of ethanol (2.4 g/kg) have been compared in four subpopulations of mice that differ pairwise in brain weight. One pair of subpopulations has been isolated from the hybrid group and the other, from generation 22 of selection of the parental strains. The results of ANOVA have demonstrated that brain weight is related to the response to ethanol injections. The parameters of stereotyped behavior, which increased in after ethanol injections and reflected the decrease in exploratory activity) were different in mice with high and low relative brain weights. The pattern of behavioral changes after ethanol injections is the second (after increased learning ability) behavioral trait found to be correlated with brain weight.

Nociceptive thresholds in the tail-flick test decreased in adult 2.5-month-old KM, Wag/Rij, and Wistar rats receiving injections of placebo in the neonatal period (days 3-9 of life).

Mice selected for large and small brain weight preferred to move rightwards in two cognitive paradigms, food-motivated T-maze performance and extrapolation ability tests. The degree of asymmetry in choices of movement direction varied in selection generations and sometimes was accompanied by asymmetry in the weight of the left and right hippocampi and other forebrain structures and different numbers of right and left neocortical cells.

Mice of two strains selected for small and large brain weight (SB and LB, respectively) had free access to 10% alcohol and water within three months. At the end of this period, they consumed alcohol in daily dose of 6.9 +/- 0.9 and 7.5 +/- 0.8 g/kg, respectively. After a period of imposed three-day abstinence, the alcohol consumption by the mice of these strains increased by 68.6 and 49.3%, respectively. Exploratory behavior of independent groups of mice from these strains was studied in the closed cross-maze. The animals were injected with ethanol (2.4 g/kg, i.p.) or vehicle twice with a weekly interval. In SB mice, the first ethanol administration increased the total time of maze exploration and the number of stereotyped visits. The second ethanol administration did not increase the time of exploration but increased the number of stereotyped visits even to the greater extent. The latter indicates the development of rapid tolerance and sensitization of these behaviors to the drug, respectively. The ethanol administration inhibited exploratory patrolling behavior and defecations. In LB mice, both the first and second ethanol administrations increased the number of stereotyped visits and decreased the exploration time and the number of defecations. The results do not support the psychomotor stimulant hypothesis of alcohol addiction. It is proposed that SB and LB mice may serve as models for Cloninger's types 1 and 2 alcoholics and may be useful for investigation of neuropharmacological mechanisms of stimulatory and inhibitory effects of ethanol.

We studied cytoarchitectonics of the hippocampus in 101/HY and CBA mice on brain sections stained after Nissl and Timm. In CBA mice, the structure of hippocampus was normal. In 10/HY mice, stratum pyramidale in field CA3 was "splitted" and the density of pyramidal neurons was decreased. Abnormalities were also found in the zone of suprapyramidal projections of mossy fibers (sp-ME), i.e., terminals of axons of the fascia dentata granular cells on the apical dendrites of pyramids. If in CBA mice the sp-MF zone was normal, i.e., looked like a vast compact formation or dense ordered bundle, in 101/HY mice, the sp-MF zone represented a group of scattered, diffuse, and interrupted bundles of varying length, some of which were incorporated in stratum pyramidale. Possible causes of the described morphological abnormalities are discussed, as well as their relation to specific features of biology, behavior, and neurological status of 101/HY mice.

Previous behavioral studies (Minichiello et al., Neuron 1999;24:401-414) showed that mice deficient for the TrkB receptor in the forebrain were unable to learn a swimming navigation task with an invisible platform and were severely impaired in finding a visible platform in the same setup. Likewise, additional behavioral deficits suggested a malfunction of the hippocampus and proximally connected forebrain structures. In order to discriminate whether the behavioral impairment was caused either by deficits in spatial memory and learning, or alternatively by loss of behavioral flexibility, 8 trkB mutant, 13 wild-type, and 22 heterozygous mice were implanted with transponders and released for 21 days into a large outdoor pen (10 x 10 m). The enclosure contained 2 shelters and 8 computer-controlled feeder boxes, delivering food portions for every mouse only during their first visit. Every third day, mice received food ad libitum inside the shelters. All mice learned to patrol the boxes correctly within a few days. However, significant differences emerged during those days with free food available. Wild-type mice remained inside the shelters, while all homozygous mutants continued to patrol the boxes in their habitual way, the heterozygous mutants showing intermediate scores. These and previous data suggest that one of the natural functions of the mouse hippocampus is to comediate behavioral flexibility, and that TrkB receptors might play an essential role in maintaining the neuronal short-term plasticity necessary for this capacity.

1. Several behavioral tests were used to compare two lines of mice selected for large (LB) and small brain (SB) weight on the basis of brain/body weight ratio values. 2. An elevated pain sensitivity as well more intense startle response was shown in SB mice in comparison with LB mice. 3. In inescapable situations of slip funnel and tail suspension tests, analogues of the Porsolt swim test, higher immobility scores in SB mice suggest an increased level of fear and/or anxiety the stress situations. 4. The SB mice demonstrated higher levels of locomotion in open field and cross-maze tests. In the latter test, the SB mice also showed increased tendency for stereotyped alternation of two arms during maze exploration. 5. Acute administration of a moderate dose of ethanol (3 g/kg) had opposite effects on the total time of cross-maze exploration: this measure increased in the SB and decreased in the LB line. By contrast, the tendency for stereotypy was similarly increased and the efficacy of maze exploration decreased in both lines.

Studies of behavior, neurophysiological reactions, neuromediator synthesis and brain structure of mice of the 101/HY strain (including those of the authors) are reviewed. This mouse strain is characterized by a chromosomal instability because of a recessive mutation mutator-1 (mut-1) and the defective DNA excision repair. Experimental studies revealed a number of behavioral and neurological deviations in the 101/HY as compared to the CBA and the C3H strains. These are abnormalities in spatial orientation, altered fear and anxiety reactions, anomalous locomotion, seizure developing in response to agents of various nature, and disturbances of the central nervous system, both structural and biochemical. Genome instability results in a number of neurological mutations, that may lead to the phenotypical effects observed in the 101/HY mice. Since the 101/HY mice partially display signs of severe human hereditary diseases caused by chromosomal instability and defective DNA repair, they can serve as a promising genetic model for these and other diseases related to impairment of the central nervous system.

Neonatal injection of the ACTH4-10 fragment (5 micrograms daily for five days) caused genotype-dependent changes in concentrations of some monoaminergic neuromediators and their metabolites in hippocampus and brain stem of adult CBA and 101/HY mice. The catecholaminergic neurons increased in number in hypothalamic zona incerta of adult 101/HY mice. Neonatal injection of the peptide caused also genotype-dependent changes in the exploratory behavior of adult animals. Sound sensitivity was reduced in the 101/HY mice, whereas no sensitivity was revealed in both control and experimental groups of the CBA mice. The effects discovered were suggested to be caused by changes in neuronal differentiation.

Free-living female laboratory mice, adapted to outdoor life in large pens providing a naturalistic environment, were tested for their ability to modify their foraging habits to controlled food supply. An automatic feeder box delivered a small portion of the daily quantity of seeds to each individual mouse. Eight such boxes were placed into an outdoor pen. Each day, mice had to visit all boxes to gather the daily amount of food and were rewarded only at the first visit to each box. Mice were individually recognised by an implanted microchip. Throughout a 16-day period, feeding activity concentrated in an interval time around the beginning of the daily session. During the same period, the number of different feeders visited every day by mice increased irrespective of variation in exploratory activity. The experimental set-up allowed detecting temporal and spatial adaptations to the food restriction, as well as behavioural differences due to territorial and social factors. These data permit the design of novel tests assessing behavioural changes, memory and learning in normal and genetically modified mice, both in the laboratory and in naturalistic settings.

A review of the papers published in the Journal of Higher Nervous Activity dedicated to behavioral and neurophysiological studies carried out using the genetic approach is presented. The review is based on classification, which subdivides the diversity of behavioral phenomena into three large categories: instinctive, acquired behavior, and elementary reasoning phenomena. The main contribution to these publications was made by researches at the Institute of Cytology and Genetics, Russian Academy of Sciences, Siberian Branch (Novosibirsk), Institute of Physiology, Russian Academy of Sciences (St.-Petersburg), and Department of Physiology of Higher Nervous Activity, Biological Faculty, Lomonosov State University (Moscow). The traditional lines of investigations are: behavioral and neurochemical consequences of domestication, numerous physiological correlations in rat strains selected for high and low excitability levels, and genetic studies of animal reasoning.

Emotionality, anxiety and stress reactivity were studied in mice selected for large (LW) and small (SW) brain weight. The open-field test, startle reaction, cross-maze, tail suspension and slippery funnel tests were used. It was shown that the SW mice are more active in the open field, more anxious and predisposed to the stereotyped behavior and passive reactions in stress situations. The relationship between the studied traits and brain weight and their influence on cognitive behavior are discussed.

We have identified interstrain differences in the rate of formation of certain reflexes and parameters of physical development in CBA/LacSto and 101/HY mice. We have shown that in young 101/HY mice, the maturation of reflexes reflecting the development of the vestibular, neurosensory, and neuromuscular systems, such as surface righting, bar holding, negative geotaxis, and auditory startle response, takes place later during postnatal life. Opening of eyes and auditory canals in mice of all studied groups takes place at the same time. In CBA females, maturation of cliff avoidance reflex occurs later than in 101/HY females; hair also appeared later. Body weight of young 101/HY mice of both sexes is significantly higher during the period of postnatal development from day 2 to day 20 than in the CBA strain. However, the relative brain weight was lower in the 101/HY strain. CBA males had a higher brain weight and also showed a faster rate of formation of inborn reflexes. We discuss possible factors underlying the observed difficulties in the rate of formation of reflexes in 101/HY and CBA young mice in relation to general background information about their genetic and neurobehavioral features. The results provide evidence that these differences are genetically determined; the rate of reflex formation does not depend on the overall physical development of mice and is rather due to a delay and/or abnormalities in nervous system development.

The capability for extrapolation of movement direction of stimuli and learning ability in T-maze were studied in F15-F18 mice generations, selected for large (LB) and small (SB) brain weight. There were no significant or stable differences between strains in capacity for extrapolation. Learning ability was higher in mice of the LB strain. In these mice, the behavioral asymmetry (the tendency to move to the right) was observed during performance of both extrapolation and T-maze tasks. Since such an asymmetry was absent in mice of initial heterogeneous population, we think that the observed phenomenon may be a concomitant result of brain weight selection. The described strains present a model for studying the functional relationships between brain weight and behavior.

Mice selected for large and small brain weights (LB and SB strains, respectively) were tested for audiogenic seizure sensitivity. We have examined 150 LB and 120 SB mice of the 13th and 14th generations. In mice of the 12th generation brain and body weight values were 498.6 +/- +/- 2.1 mg and 26.2 +/- 0.4 g, respectively, for the LB and 415.35 +/- 1.9 mg and 23.8 +/- 0.3 g for the SB, the difference being significant for both values (p < 0.001). The SB mice revealed higher audiogenic sensitivity (larger proportion of seizures and deaths) at the age of 22-27 days. Adult LB mice were more sensitive than SB of the same age (irrespective of whether they received priming stimulation or not). The obtained evidence is discussed in the context of differences between audiogenic fits and other seizure states.

The seizure sensitivities to pentylenetetrazol (Ptz, 25-100 mg/kg) and strychnine (S, 2 mg/kg) were tested in two mice lines selected for large (LB) and small (SB) brain weight (brain weight difference being approximately 75 mg). The selection was based on a regression line connecting body and brain weight. SB mice were more sensitive to both drugs-their seizure latencies were shorter and lethality higher than in LBs. The seizures generated by Ptz and S are known to affect different neurotransmitter systems. The interstrain differences in seizure susceptibility are probably determined by SB mice nervous system traits rather than by differences in the particular neurochemical trait. The data on neocortical cytoarchitectonics obtained during our previous brain selection experiment could serve as the indirect evidence favouring such a suggestion.

The results of two experiments on selection of laboratory mice for large and small brain weight are presented. Selection was based on the regression relationship between body and brain weight. This allowed considerable differences in brain weight to be obtained accompanied by insignificant interlinear differences in body weight compared to the range of intralinear variation. The two lines of mice with a large and small brain weight (F9-F10) differed significantly in brain weight. The absolute difference was 60-70 mg, i.e., approximately 13% of the brain weight in the original heterogeneous population.

We found that the administration of ACTH4-10 fragment to newborn mice of several strains (DBA/2, CBA, C57BL/6J, CBARb, and BLRb) for 5 days from the second day of life led to changes of several behavioral characteristics of adult animals. The effect of peptide administration on exploratory behavior of mice and on following the direction of stimulus movement are opposite to those induced by pain stimulation, i.e., administration of a solvent. The results are interpreted as a possible antistress effect of the peptide, which is realized during the period of neurodifferentiation. These data are discussed in terms of a possible effect of the used peptide on differentiation of the nervous system.

It has been established that mice of strain 101/HY suffer from audiogenic epilepsy seizures, the frequency and severity of which depend on animal sex and age. Mice were subjected to high intensity sound (about 100 dB) at the age of 14-16, 30, 60, and 190-270 days (Groups I, II, III, and IV, respectively). The testing was done three times. Mice of Group I were tested twice. The duration of sound stimulus was 20 s. Mice of both sexes from Group I were most sensitive. During the first test, the so-called "wild-run" behavior developed in 90% of animals and 60% showed tonoclonic seizure. Lethal outcomes in animals of this group (26.7% of the males and 23.5% of the females) were observed mainly during the second test, conducted one day after the first one. Only 6.7% of the males died during the first test in Group I. Severity of audiogenic seizure in males decreased with age, whereas among females there was a decrease in the number of animals with sensitivity to the sound stimulus. Among females of Groups III and IV, we did not detect any animals responding to the audiogenic stimulus by seizure and there were no deaths. Mechanisms underlying the audiogenic sensitivity of 101/HY mice are reviewed in the light of other information about the development of this genetic trait in rodents and in connection with other biological characteristics of these animals.

Learning abilities of mice selected by the small and large brain weights were studied in Y-maze. Thirsty mice were trained to find water in one of the maze arms. The minimal latency of this reaction reached in the process of learning was shorter in the mice selected by the heavy brain. Benzaldehyde which is commonly supposed to be an aversive olfactory stimulus being presented before drinking sharply increased the latency, nevertheless, it remained shorter in mice with heavy brain. The response to the aversive stimulus varied between the individuals, especially in mice selected by the small brain weight.

C57BL/6J (B6) and CBA mice with normal karyotype and respective substrains carrying robertsonian translocation (fusion) of chromosomes 8 and 17 (Rb) were compared in their ability to extrapolate the direction of stimulus movement disappearing from the field of vision, rearings and hole-poke responses, and exploration strategies in a plus-maze. Rb mice were shown to be superior to normal karyotype groups in extrapolation behaviour. The pattern of interstrain differences in noradrenaline level in the cortex and serotonin turnover indices in the hippocampus correlated with differences in extrapolation ability, while exploration strategies in the plus-maze correlated with differences in dopamine level and its turnover rate in the neocortex and striatum. The data demonstrated that chromosomal rearrangement inducing behavioural differences was accompanied also by discrete neurochemical changes, and that spatial exploration strategies (being probably the constituent of general spatial abilities of mice) were to a large extent independent from extrapolation ability which was regarded as the index of animal reasoning capacity.

Females of strains 101/HY and CBA were treated with a single dose of thio-TEPA (0, 0.625, or 1.25 mg/kg body weight) on day 12 of gestation (deposition of a vaginal plug was considered as the first day of gestation). Special experiments were performed on their offspring at 3 months of age to study exploratory-research activity (burrow reactions, upright postures), locomotor activity in a "open field" cage, emotional reactivity, and level of feeding motivation. Changes in behavior after exposure to thio-TEPA were observed in mice of both sexes and genotypes; however, in 101/HY mice, which are characterized by genetically determined genome instability and a defect in DNA repair system, such changes were more pronounced. In general, they may be defined as a decrease in intensity of exploratory-research activity with some modulation of the level of motor activity. Sex differences in behavior of animals of both strains after prenatal exposure to thio-TEPA were also found. The data provide evidence about the specific role of genetic factors in variation of mouse behavior after prenatal exposure to thiophosphamide and allow consideration of thio-TEPA as a behavioral teratogen.

Female mice from inbred strains carrying a Robertsonian translocation (nine CBARb and eight C57BL/6Rb) were compared with animals from their respective strains (seven CBA and nine C57BL/6) first in open-field activity (two exposures of 10-min duration), then during 5 days (with six trials each) in Morris' swimming navigation test, and finally, in their ability to extrapolate the future position of a food reward being moved slowly out of their reach. ANOVA (strain and translocation) revealed significant effects of Robertsonian translocations (Rb) in swimming navigation, Rb mice being impaired primarily in the initial phases of acquisition and during the first trials of platform reversal and the impairment being stronger in C57BL/6 mice. In the open field, Rb mice were as active as the normal strains but showed significantly increased path tortuosity and moved slightly faster. In the extrapolation task, Rb mice showed above-chance levels in moving to the target indicated by the disappearance of the stimulus, while normal mice chose at chance levels, but the translocation effects were not statistically significant. These data indicate that telocentric fusion of chromosomes may entail behavioral alterations, perhaps by subtle changes in neurotransmitters or limbic circuitry. The expression of such alterations, however, can be remarkably strain dependent.

This paper reviews the investigations of Prof. L. V. Krushinsky and his colleagues into the genetics of complex behaviors in mammals. The ability of animals to extrapolate the direction of a food stimulus movement was investigated in wild and domesticated foxes (including different fur-color mutants), wild brown rats, and laboratory rats and mice. Wild animals (raised in the laboratory) were shown to be superior to their respective domesticated forms on performance of the extrapolation task, especially in their scores for the first presentation, in which no previous experience could be used. Laboratory rats and mice demonstrated a low level of extrapolation performance. This means that only a few laboratory animals were capable of solving the task, i.e., the percentage of correct solutions was equivalent to chance. The brain weight selection program resulted in two mice strains with a 20% (90-mg) difference in brain weight. Ability to solve the extrapolation task was present in low-brain weight mice in generations 7-11 but declined with further selection. Investigation of extrapolation ability in mice with different chromosomal anomalies demonstrated that animals with Robertsonian translocations Rb(8,17) 1lem and Rb(8,17) 6Sic were capable of solving this task in a statistically significant majority of cases, while mice with fusion of other chromosomes, as well as CBA normal karyotype mice, performed no better than expected by chance. Mice with two types of partial trisomies and animals homo- and heterozygous for translocations were also tested.(ABSTRACT TRUNCATED AT 250 WORDS)

An unusual type of locomotion--backward movements--was revealed in the 101/HY mouse strain characterized by a chromosomal instability and the defect in DNA repair. The backward movements were found in 60% of mice belonging to the population under study. The manifestation of the character was found to vary: it was high in 16% of the animals. No age and sex differences were found. The backward movements in the 101/HY mouse strain were somewhat similar to the peculiarity in locomotion of the neurological hot-foot mouse mutants. The latter had mild anatomical alterations in the cerebellum. No obvious brain pathology was revealed in the 101/HY mice.

Laboratory mice with Robertsonian translocation Rb(8,17)1Iem, mice of CBA substrain with the same translocation as well as CBA normal karyotype mice were investigated in several behavioural tests, their results being analysed by means of factor analysis. The genetic differences were revealed in the patterns of factor loadings, in particular in factors "feeding behaviour structure" and "weight loss". The behaviour of mice during logic problem solving (the ability to extrapolate the direction of food stimulus movement was tested) proved to be genotype-dependent in respect to connections with exploratory behaviour indices. Tendencies towards stereotypic or variable (plastic) behaviour patterns were revealed in CBA mice and mice with Rb(8,17)1Iem mice respectively.

Anosmia induced by intranasal zinc administration to mice capable of solving an extrapolation problem (search for food which disappears from animal sight in definite direction), led to disturbance of normal food searching behaviour. In anosmic mice the percentage of task solutions (correct as well as incorrect) in which the trajectory was the shortest ("goal-directed"), was significantly lower than in controls. At the same time the percentages of correct "goal-directed" choices were equal in both groups. The main differences in the number of correct task solutions were among those trials in which non-goal-directed behaviour was delivered. Thus zinc induced anosmia provokes rather severe deteriorations of food searching behaviour. The investigated group of mice possessing Robertsonian translocation Rb(8, 17) 1 IEM, reveals no disturbance of extrapolation capacity during first 20 s after task presentation. This signifies that this capacity which in this group is higher than in other mice, is not determined by peculiarities of their olfaction.

The ability of laboratory mice to learn to solve a simple food searching task, and their ability to extrapolate the direction of stimulus movement, were investigated in animals of CBA inbred strain (64 mice) and in mice with Robertsonian fusion of 8 and 17 chromosomes -- Rb (8, 17) 1 IEM possessing different genetic background (122 mice). As the ability for extrapolation is tested while the animal has no previous experience of such task solving, this form of behaviour seems to be different from conditioning. Mice with Rb (8, 17) 1 IEM but not CBA mice proved to be capable to solve the extrapolatory task at its first presentation. Their learning ability was found to be also superior to that of CBA mice. The present data proved that mice with Rb (8, 17) 1 IEM translocation may serve as a very promising model for investigation of complex behaviour patterns.

Laboratory mice possessing Robertsonian translocation Rb (8, 17) 1IEM in their karyotype, reveal statistically significant ability for extrapolation of the direction of stimulus movement which disappears from animal's view. Inbred CBA mice with the same translocation are less capable, and CBA mice with normal karyotype are totally incapable of solving this task. Cortical noradrenaline levels in mice with Rb (8, 17) 1IEM were the lowest and brain stem levels the highest among the three groups investigated. Serotonin levels reveal no changes among these groups.

Solution of an extrapolation problem was studied on 28 albino rats (Way strain and laboratory population) and 68 hybrids (the first generation) of wild and laboratory rats in experiments with a screen--the search of food after the disappearance of the food stimulus from the animal's sight. Administration of caffeine (20 mg/kg) and d,l-amphetamine (0.1 mg/kg), though not changing the share of correct solutions, diminishes the number of "refusals" to solve it. Increased motor activity and diminished emotionality of the rats due to administration of the drugs, recorded in an open field test, are likely to cause a decrease in the number of refusals. Administration of d,l-amphetamine facilitates the process of conditioning which contributes to the greater number of positive solutions of the repeatedly presented task.