Synchronization of the Estrous Cycle against the Background of Increased Excitability in Rats Selected for Catatonic Type of Reaction.

Selection for the elevation of catatonic type of reaction in female GC rats ("genetic" and "catatonia") was followed by an increase in the number of intense running episodes in response to acoustic stimulation. The observed changes are typical of increased general excitability in these animals. The phenomenon of estrous cycle synchronization was confirmed by variations in the concentrations of estradiol and progesterone in groups of Wistar and GC rats differing by the degree of synchronization. Some differences were found in the concentration of main sex hormones in the blood from female GC and Wistar rats.

[Comparative analysis of imipramine intake reactions in catatonic and wistar rats].

Chronic imipramine intake (7.5 mg/kg) leads to the stable decrease of excitable reactions to sound stimulant in Wistar rats and induced phase behavioral response in catatonic GC rats. Increased noradrenaline level in frontal cortex and striatum in Wistar animals was shown, whereas it didn't reveal noradrenaline level differences in any brain structures in GC rats. The higher blood corticosterone concentration was decreased under antidepressant reaction in GC rats. Differences between intact GC animals were found out: reduced triglyceride level, lesser body weight, and greater weight index of adrenals in comparison with Wistar rats. Various mechanisms of imipramine action in two rat strains were shown: influence on adrenergic brain system, taking part in the control of exiting behavior in Wistar rats and reaction in adrenals in GC rats.

[Selection for catatonic reaction in rats: a study of interstrain differences by magnetic resonance imaging].

Brain studies by magnetic resonance imaging, angiography, and spectroscopy have been performed with rat strains Wistar, GC (genetic and catatonia), and PM+ (pendulum movements). Both GC and PM+ rats show similar deviations from the ancestral Wistar population in having smaller areas of the right striatum (coronal slice). The anterior horns of lateral ventricles in GC rats are smaller than in the control strain. The maximum blood flow velocity in the common carotid arteries of PM+ rats is greater. The GC and PM+ strains differ in myo-inositol level in the hippocampus. The PM+ strain is characterized by a lower taurine level in the hippocampus, which may be one of the participants regulated the predisposition to audiogenic seizures.

[The increase in the proportion of nervous animals bred for catatonia: the participation of central adrenoreceptors in catatonic reactions].

Using a large amount of breeding material, the idea of D. K. Belyaev on the role of selection in the appearance of new behavioral and neuronal forms was confirmed. Experiments were performed using rats of the GC (genetics + catatonia) strain, which are prone to passive defensive reactions of cataleptic freezing. At the current breeding stage, elevation of the proportion of so-called nervous animals was demonstrated, both with respect to the expression of such reactions and their frequency. At this breeding stage, in the brains of GC rats, the mRNA levels of alpha1A- and alpha2A-adrenoreceptor genes were determined. A decrease of alpha1A-adrenoreceptor gene expression in the midbrain and medulla oblongata, along with elevation of alpha2A-adrenoreceptor gene expression in the frontal cortex was observed. It was suggested that changes in the expression of alpha-adrenoreceptor genes could be caused by an increase in the proportion of nervous animals and could contribute to the akinetic behavioral component in GC rats.

Effect of imipramine on nerve excitability in GC rats.

Imipramine test (7.5 mg/kg) revealed a persistent positive reaction of Wistar rats, which manifested in reduced excitability of animals. Oral administration of imipramine solution was followed by unstable behavioral reactions in GC rats. Norepinephrine concentration in the cortical and limbic regions of these animals remained unchanged, while plasma corticosterone concentration decreased to the control level and did not differ from that in Wistar rats. Our results indicate that imipramine has a modulatory effect on destabilization of the adaptive system in catatonic GC rats.

[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.

[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.

[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.

[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).

Some physiological manifestations of the activity of the gene controlling the predisposition to pendulum-like movements in rats.

The physiological actions of the gene controlling the predisposition to stereotypic hyperkinesia in the form of pendulum-like movements (PM) and, probably, a form of spontaneous nystagmus in rats with albinism are manifest as a number of behavioral characteristics (total motor activity, emotionality, startle reflex intensity, sensitivity to serotonin 5-HT2 receptors as assessed in terms of the intensity of head twitching, and predisposition to cataleptic responses). A number of parameters showed differences between hybrids of gray handling-tolerant rats and carriers of the PM gene on the one hand, and between gray rats and animals not carrying the PM gene on the other. Some behavioral characteristics of rats with PM were closer to those of Wistar rats than to those of rats without PM. This, as well as the high frequency of PM in Wistar rats, indicates that the gene responsible for the manifestations of PM is not pathological, but controls a variety of adaptive features of the nervous system. The interaction between PM and the predisposition to catalepsy is biphasic in nature and is described by a curve in the form of an inverted U.

[The action of neuroleptics on different types of catalepsy in rats with a genetic predisposition to catatonic reactions]. / Deistvie neiroleptikov na razlichnye tipy katalepsii u krys s geneticheskim predraspolozheniem k katatonicheskim reaktsiiam.

Rats of GC strain with genetic predisposition to cataleptic reactions bred from Wistar rats are more sensitive to cataleptogenic effect of haloperidol and trifluperidol than Wistar rats. At the same time, chlorpromazine and sulpiride considerably shorten the time of maintenance of imposed vertical cataleptic postures for which GC strain has been selected. This paradoxical situation is interpreted so that the more pronounced neuroleptic-induced catalepsy in GC rats is caused by increased sensitivity of postsynaptic dopamine D receptors in the striatum, while the predisposition to the cataleptic postures attenuated by neuroleptics is associated with dopaminergic hyperactivity of the mesolimbic system.

[The neurohormonal characteristics of rats selected for the duration of the passive defense reaction and for the threshold of neuromuscular excitability]. / Neirogormonal'nye kharakteristiki krys, selektsionirovannykh po dlitel'nosti passivno-oboronitel'noi reaktsii i porogu nervno-myshechnoi vozbudimosti.

Two strains of rats, "genetic catalepsy" and "low-threshold", simulating some human psychopathological symptoms, were compared. Levels of brain monoamines and blood corticosterone and testosterone showed no common features in the strains studied. The levels of dopamine in amygdala and testosterone blood levels in rats of the two strains significantly deviated in opposite directions from corresponding controls. In "genetic catalepsy" strain noradrenaline content in striatum and diencephalon was decreased, and serotonin striatal level was increased.