O. V. Perepelkina

Exploratory behavior of F2 crosses of mouse lines selected for different brain weight: a multivariate analysis.

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.

Selection of mice for high scores of elementary logical task solution

52 Genetic studies on the capacity of laboratory rodents for solving cognitive tasks are mainly based on the estimation of differences between the strains [8] and the changes in this ability after manipulations with the genome of laboratory mice [7]. In spite of much interest in studies on the role of the genotype in deter mination of cognitive capacities in rodents, no attempts have been made to select animals for higher capacity of performing these tasks. Among the cogni tive tests is the ability to perform the extrapolation task. This task estimates whether the animal can find a food reinforcement that has disappeared from its’ view by “extrapolating” the future position of the food rein forcement and, for this purpose, move in the appropri ate direction and approach the food. This ability revealed intraspecific variability [3]; however, an attempt to select rats for higher expression of this capacity was unsuccessful due to increased anxiety in these rats, which prevented their use for testing.

Genotype-Dependent Changes in Pain Thresholds in Adult Mice after Neonatal Treatment

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.

[Neonatal injections of pharmacological agents and their remote genotype-dependent effects in mice and rats].

Experimental data were reviewed which demonstrated that the neonatal injection effects of certain biologically active drugs (ACTH4–10 fragment and its analogue Semax, piracetam, caffeine, levetiracetam, busperone, etc.) could be detected in adult animals as changes in physiological and behavioral reactions and in several morphological traits as well. Audiogenic seizures proneness, anxiety-fear and exploration behavior as well as pain sensitivity were analyzed. The remote effects discovered were either similar in direction to those applied to an adult organism, or opposite to it. Pharmacological treatments of such type presumably interfere the CNS development during early postnatal ontogeny and change the normal pattern of brain development. These modulatory influences could be due to changes in neurotransmitter system development and are presumably capable to induce CNS morphological deviations (numbers of neurons, adult neurogenesis).

Effect of chronic fluoxetine treatment on audiogenic epilepsy, symptoms of anxiety and depression in rats of four lines.

Anxiety (Anx) and depression (Dp) levels were evaluated in rats of 4 lines: 2 of them (KM and “4”) exhibited audiogenic seizures (AS), and 2 (Wistar and “0”) had no AS. In KM rats (with AS), Anx and Dp levels were higher than in Wistars (without AS), while in “4” and “0” rats with the related genetic background but contrasting in AS severity, Anx and Dp indices were not different. Fluoxetine treatment exerted antidepressant effect in all rat lines irrespective of its effect on AS. Thus, phenotypic expression of AS is not directly associated with the mechanisms of Anx and Dp development.

Audiogenic Epilepsy in Mice with Different Genotypes after Neonatal Treatments Enhancing Neurogenesis in Dentate Gyrus

Pups of Wistar and KM rats (with predisposition to audiogenic epilepsy) were daily injected with neuropeptide semax (50 mg/kg) or NO-synthase inhibitor L-NAME (50 mg/kg) on days 7-11 of life. Alterations of audiogenic seizures pattern were revealed in rats of both strains at the age of 1 month, while changes in seizure severity were genotype-dependent. Both agents enhance neurogenesis in the dentate gyrus of the hippocampus and the delayed effect in the form of altered seizure pattern seems to be determined by this factor. Genotype-dependent alterations of seizure severity after administration of semax and L-NAME were differently directed. These effects are suggested to be underlined by physiological and biochemical mechanisms not related to the intensity of postnatal neurogenesis.

Audiogenic epilepsy in young mice of different strains after neonatal semax treatment

Neonatal (from day 2 to day 7 of life) injection of neuropeptide semax to mice of 5 inbred strains significantly reduced predisposition to audiogenic epilepsy in only one-month-old DBA/2J mice, which manifested in changes in the mean audiogenic sensitivity score and percentage of animals dead as a result of acoustic stimulation.

Neonatal administration of buspiron causes changes in intermale aggression of adult mice.

In studies on the long-term effects of neonatally administered biologically active compounds, the main attention is paid to either “socially important” substances (for example, cocaine and ethanol) or pharmaceutical drugs. In this study, long-term effects of buspiron injected to young laboratory mice were analyzed. Buspiron is an agonist of postsynaptic 5-HT1A receptors, the anxiolytic and aggression-inhibiting effect of which on adult mouse behavior was described earlier [4, 8, 9]. This effect is caused, presumably, by an increase in the level of serotonin in brain [3], because aggression intensity is known to depend on the activity of the serotonergic cerebral system [1, 7]. Therefore, we supposed that treatment of the neonatal brain modulates the function of the serotonergic system and this effect may be detected in adult animals on the basis of changes in their aggression behavior.

Correlation between Brain Weight and the Pattern of Behavior Changes in Response to Ethanol Injections in Laboratory Mice

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 derived 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 behavioral 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.

Survival under conditions of environmental stress: Variability of brain morphology and behavior in the house mouse

Two populations of laboratory mice lived outdoors in open pens for two years. Thereafter, some of them were bred in the laboratory. Morphometric analysis showed that the size of the synaptic projection area of mossy fibers (in the CA3 region of the hippocampus), which has an important functional role, and some behavioral traits of the open-pen mouse progeny had significant genetically determined differences from those in the initial population. This was attributed to differential breeding accounted for by the influence of severe environmental factors. Under environmental stress, selection occurred in the population and the mice with behavioral and neuromorphological characteristics differing from those of the control group proved to be better adapted to such conditions.