[Monoamines and function of the ovaries in rats selected for elevated catatonic reactivity].

Levels of dopamine (DOPA), noradrenalin (NA), and serotonin in hypothalamus and function of ovaries (folliculogenesis) were studied at various estrous cycle stages of the rat GK line selected for elevated catatonia. The control was the outbred Wistar line. Selection for elevated catatonia led to a decrease of the number of all cell types in GK ovaries in diestrus and proestrus. In estrus of the GK females, on the contrary, there was a tendency for an increase of the number of the growing follicles as compared with Wistar females. On the background of a decrease of the DOPA and NA content in hypothalamus of the GK line rats, the higher catecholamine level was observed in estrus and the lower--in diestrus. Thus, selection for manifestation of the excessive protective catatonical type of reaction in the form of an increase of duration and intensity of freezing involves the monoaminergic brain system and leads to delay of folliculogenesis that is the key factor in regulation of fertility.

Monoamines and sexual function in rats bred for increased catatonic reactivity.

Body weight, ovary and uterus weight, the nature of estral cycles, and hypothalamus dopamine and noradrenaline levels and plasma testosterone levels were studied in female GC rats, bred for increased catatonic reactivity, at different stages of the estral cycle (estrus, proestrus). The outbred Wistar strain served as controls. On the background of decreased body weight, GC females showed impairments to the morphological cyclical changes in the ovaries and uterus, with a reduction in ovary weight in diestrus (p < 0.01) and a smaller estrogen-dependent increase in uterus weight in estrus as compared with Wistar females. On the background of decreases in dopamine and noradrenaline contents in the hypothalamus, GC rats showed higher levels of these monoamines in estrus and lower levels in diestrus. Plasma testosterone levels in female GC rats were higher in diestrus than in estrus and in Wistar rats.

[Learning of rats predisposed to catalepsy in Morris water test].

It was shown that GC rats predisposed to catalepsy do not differ from Wistar rats in success rate or latency (time of finding of the hidden escape platform) in the Morris water test. However, unlike Wistar, GC rats are inclined to passive drift and longer floating episodes. Rats of the MD+ strain predisposed to hyperkinesis in the form of horizontal pendulum-like movements of the head and upper limb girdle show longer latency and lower rate of successful trials than Wistar or MD-, rats selected for absence of the pendulum-like movements.

[Monoamines and reproductive function of rats selected for strengthening of catatonia response].

Weights of the body, ovaries, and uterus; estrous cycles and the contents of dopamine (DA) and norepinephrine (NE) in the hypothalami, and testosterone in blood plasma of GC females were studied at various estrous stages (diestrus and estrus). The outbred Wistar line was used as a control. In addition to reduced body weight in GC females, we observed disturbed morphological cyclic linkages between the ovaries and uterus: ovary weight reduction in diestrus (p < 0.01) and lower estrogen-related increase in uterus weight in estrus in GC females in comparison with Wistar ones. While the contents of DA and NE in GC hypothalami were reduced, the levels of these monoamines were high in estrus and low in diestrus. Testosterone levels in GC female plasma in diestrus were higher than in estrus or in Wistar rats.

Genetic catalepsy and ultralow dose antibodies to S-100B antigen.

We studied consumption of 20% sucrose solution by rats genetically predisposed to catalepsy (GC strain) during training. The consumption of sucrose solution by GC rats was lower in comparison to that in Wistar rats. "Potentiated" antibodies to S-100B antigen administered orally after training sessions increased the number and duration of subsequent contacts of rats with sucrose solution.

[Confirmation of a positive genetic relationship between pendulum movements, audiogenic epilepsy, catalepsy, and "nervousness" in rats].

Relationships between the predispositions to pendulum movements (PMs), catalepsy, and audiogenic epilepsy in the course of breeding for "nervousness" and freezing have been studied. A positive genetic relationship between PMs, catalepsy, and audiogenic epilepsy has been demonstrated. Eighty to ninety percent of rats selected for enhanced PMs (strain PM+) exhibit predisposition to audiogenic seizures, whereas this frequency in the PM-free strain (PM-) is 10-40%.

[Typological characteristics of behavior in strains of rats bred for enhancement and absence of pendulum movements. Association with brain monoamines].

Typological characteristics of behavior were studied in rats bred for enhancement (PM+) and absence (PM-) of pendulum movements. Excitement in different test situations was manifest in PM+ rats, whereas passive defensive reactions were characteristic of PM- rats. Increased excitability of PM+ rats was expressed in their greater predisposition to audiogenic epilepsy (83% in PM+ versus 40% in PM- rats). On the contrary, PM- rats were found to be more prone to freezing (61% in PV- versus 11% in PM+). In PM+ rats, noradrenaline and serotonin contents were decreased in hypothalamus (as compared to PM- and control Wistar stain), whereas in PM- rats, serotonin content was increased in striatum, hypothalamus and midbrain as compared to control strains.

[Catalepsy and "nervousness" in rats: results of replicated selection].

Replicated breeding during five generations from an outbred population of Wistar rats performed, in contrast to the previous breeding, differentially for predisposition to catalepsy and "nervousness" confirmed earlier data that catalepsy and "nervousness" are two phenotypic expressions of the same bipolar catatonic genotype.

[Some neuroendocrinological changes in rats of cataleptic strain GC. Influences of ontogenesis and generation of breeding].

The content of biogenic amines: dopamine, noradrenaline and serotonine, in rats of cataleptic strain GC as compared with the control strain Wistar at the age of 1 and 5 months is decreased, the maximal decrease being found in the so-called "nervous" animals. The aldosterone content was decreased at 5 month age in the GC rats. The testosterone content at the age of 1 month in GC rats does not differ from that in Wistar rats, but at the age of 5 months it was decreased as compared to Wistar, the maximal decrease being found again in "nervous" GC rats. The data obtained point to peculiarities of ontogenetic regulation and to commonness of mechanisms of catalepsy and "nervousness" in GC rats.

[Genetic analysis of the predisposition to audiogenic seizure fits in Krushinsky-Molodkina rat strain].

The expression of audiogenic seizure fits has been studied in F1 hybrids between audiogenic seizure-prone Krushinsky-Molodkina rat strain and Wistar rats not prone to audiogenic seizures, as well as in two backcross generations. Only 10% of F1 hybrids exhibit audiogenic seizure fits, whereas the frequency of this character in two generations of their backcrosses with Krushinsky-Molodkina rats is about 50%. A digenic model with incomplete penetrance has been put forward to explain the control of audiogenic seizure fits. This model fits the data obtained: the theoretically expected distributions of the character in offsprings of different crosses do not differ significantly from those observed in experiments. The model explains why the distribution of the character is the same in the first and second backcross offsprings.

[Dual manifestation of catatonic reaction in rats].

Results of genetic, neurophysiological, neurochemical and pharmacological suggest that the cataleptic freezing and "nervousness" observed in the cataleptic rat strain GC have a common mechanism. There seems to be a physiological factor causing catalepsy, upon reaching a certain level of intensity, to be transformed into "nervousness", which is observed both at different period and/or moment of individual life and in the processes of breeding the strain for predisposition to catalepsy.

Correlation between cataleptic freezing and prepulse inhibition of the startle reflex in rats.

GC rats, bred for a predisposition to cataleptic freezing, were found to show a significant negative correlation between the duration of freezing and the level of prepulse inhibition of the startle reflex. In addition, a group of GC rats characterized by increased "nervousness" also showed a negative correlation between the duration of freezing and the extent of habituation of the startle reflex. These correlations were not seen in Wistar rats. Since decreases in the level of prepulse inhibition and habituation of the startle reflex are regarded as characteristic of schizophrenia, it is suggested that cataleptic freezing in GC rats might be used as a model of schizophrenic pyschopathology.

[Catatonia or depression: the GC rat strain as an animal model of psychopathology]. / Katatoniia ili depressiia? Liniia krys GK--geneticheskaia zhivotnaia model' psikhopatologii.

The utility of "incomplete" genetic animal models of human diseases, in particular, psychoses, is discussed. The GC rat strain selected for predisposition to cataleptic reactions is described. It is shown that in many of their characteristics, GC rats are similar to schizophrenic and depressive patients. A possibility that akinetic catatonic states and depressions, hyperkinetic catatonic states and mania share common mechanisms is discussed. It is hypothesized that the GC strain may be an incomplete model of the common genetic and pathogenetic core of schizophrenic substuporous states and depression, which suggests the importance of returning to the issue of a unitary psychosis (Einheitpsychosis).

[Bipolar manifestation of cataleptic reactions in rats]. / Bipoliarnoe proiavlenie katalepticheskogo tipa reagirovaniia u krys.

Selection of GC rats for the predisposition to cataleptic freezing has increased not only the frequency, intensity, and duration of freezing, but also the proportion of irritable or "nervous" rats with enhanced anxiety, defensive behavior with vocalization, jerky running, and jumpiness. An increased amplitude of the startle reflex is a correlate of this "nervousness." The results of the comparison of some behavioral characters in the nervous and freezing GC rats, as well as in F1 and F2 offspring from homogeneous crosses between nervous and freezing GC rats suggest that cataleptic freezing and nervousness are two poles of the same bipolar catatonic reaction. They have a common mechanism, with the alternative or preferential expression of one particular form of the reaction is determined by the external and internal environments or the set of modifier genes in the given individual.

Diurnal variations in lymphocyte subpopulations in lymphoid organs of rats with genetic catalepsy and Wistar rats.

Parameters of the immune status of the thymus and spleen in rats with genetic catalepsy were lower compared to those in Wistar rats. Diurnal variations in cell subpopulations of lymphoid organs were different in animals of these strains. Behavioral characteristics and neuroendocrine state in rats with genetic catalepsy were associated with specific changes in the immune system and neuroimmune interactions.

Components of early maternal environment affecting the predisposition to catalepsy.

Reciprocal pup substitution (cross-fostering) in cataleptic GC (designated so by the initials of words "genetic" and "catalepsy") and control Wistar females resulted in attenuation of cataleptic predisposition in GC rats fostered by Wistar foster-mothers. The latter demonstrate a more intense maternal care than GC females. There was a significant negative correlation between the frequency of mother staying in nest and the duration of pinch-induced catalepsy in pups fostered by her. In the home-cage retrieval test, the females of the strains compared showed a significant dependence of the latencies of approach to, and retrieval of, pups on their own and the pups' genotype.

Effect of chronic administration of imipramine on 2A-serotonin receptor mRNA in brain cortex of rats predisposed and resistant to catalepsy.

Rats selected by predisposition to catalepsy showed decreased level of 2A-serotonin receptor mRNA in the frontal cortex in comparison with Wistar rats (p<0.05). Chronic administration of tricyclic antidepressant imipramine hydrochloride 2-fold increased the content of receptor mRNA in genetically cataleptic rats (p<0.001) and did not change this parameter in Wistar rats. These results prompted us to revise current notion on the mechanisms of chronic effect of imipramine on 2A-serotonin receptors.

Effects of thyroid hormone deficiency on behavior in rat strains with different predisposition to catalepsy.

The effects of thyroidectomy on anxiety-related behavior in the elevated plus-maze test, locomotor activity, and defecation in the open-field test and duration of cataleptic freezing were studied in rats of two strains differing in predisposition to catalepsy: cataleptic strain GC and its ancestor strain Wistar. Total thyroxine level was significantly decreased in control GC rats compared to that in control Wistar rats. Control Wistar and GC rats did not differ either in the percentages of open-arm entries or the time spent therein in the elevated plus-maze test or in defecation score in the open-field test. At the same time, control Wistar rats showed more locomotor activity compared to control GC rats in the open-field test. Thyroid hormone deficiency did not affect the percentages of open-arm entries and the time spent therein in the elevated plus-maze test as well as defecation score in both strains. Thyroidectomy did not alter significantly locomotor activity in Wistar rats, but produced a nearly twofold increase in locomotor activity in GC rats. The most important finding is that thyroidectomy significantly increased the expression of catalepsy in Wistar rats, which points to a role of thyroid hormones in the regulation of predisposition to cataleptic reaction.

[Effect of changes in the early maternal environment on predisposition to catalepsy in rats of different ages]. / Vliianie izmenenii rannei materinskoi sredy na predraspolozhennost' k katalepsii u krys v raznykh vozrastakh.

Reciprocal cross-fostering of control Wistar and catalepsy-prone GC rat pups resulted in a decrease in duration of cataleptic reactions of GC rats estimated at the age of two weeks, one month, and six months and a tendency to its decrease in Wistar rats at the age of one month. In-fostering did not exert this effect.