T. A. Alekhina

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.

Expression of the startle reaction in rats genetically predisposed towards different types of defensive behavior

The magnitudes of startle reactions, consisting of shuddering in response to acoustic signals, were studied in rats selected for predisposition to different types of defensive behavior—rats with and without passive defensive freezing reactions (catalepsy), and Norway rats selected for a lack of defensive aggression to humans or for high levels of aggression; studies were performed in an SR-Pilot apparatus. These experiments showed that expression of the startle reaction to standard sound signal in rats with a genetic predisposition to catalepsy was double that in control Wistar rats. A similar but greater difference was seen between highly aggressive and non-aggressive rats: the amplitude of the startle reaction in rats with high levels of active defenside responses was three times that in rats showing no aggression towards humans. Extinction of the reflex reaction was significantly slower in highly aggressive rats than in non-aggressive rats. A similar tendency was seen in rats with genetic predisposition to the passive defensive freezing reaction as compared with Wistar rats. It was concluded that animals with an inherited tendency to defensive behavior have higher levels of the emotional fear state, regardless of the strategy of the defensive behavior.

Catatonia or Depression: The GC Rat Strain as an Animal Model of Psychopathology

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 the unitary psychosis (Einheitpsychosis).

Bipolar manifestation of cataleptic reactions in rats

Breeding 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 S1 and S2 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.

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 α1A- and α2A-adrenoreceptor genes were determined. A decrease of α1A-adrenoreceptor gene expression in the midbrain and medulla oblongata, along with elevation of α2A-adreno-receptor gene expression in the frontal cortex was observed. It was suggested that changes in the expression of α-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.

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.

Learning in Rats Predisposed to Catatonic States in a Morris Water Maze

Studies in a Morris water maze showed that GC rats, which are predisposed to catalepsy, did not differ from Wistar rats in terms of the proportion of correct attempts or the time taken to find a platform hidden beneath the water. However, in contrast to Wistar rats, rats of the cataleptic strain tended to show passive drifting and demonstrated longer-lasting episodes of immobility in the water. PLM+ rats, which are predisposed to hyperkinesia in the form of pendulum-like horizontal movements of the head and shoulder girdle, took longer to find the platform and showed a reduced proportion of correct platform-finding attempts than Wistar rats and PLM– rats, bred for the absence of pendulum-like movements.

[Effects of monorecessive and double recessive mutations affecting coat color on the monoamine content of the brain of the American mink (Mustela vison Schreber, 1777)].

The effects of mutations affecting the coat color on the dopamine, noradrenaline, and serotonin contents of the hypothalamus and brainstem of the American mink have been studied. The sample comprised standard (+/+) and mutant minks, including the monorecessive pastel (b/b), silver-blue (p/p), and white hedlund (h/h) and the combination double recessive sapphire (a/a p/p) and pearl (k/k p/p) ones. The dopamine content of the brainstem of the monorecessive pastel (b/b) and silver-blue (p/p) minks has been found to be higher than in standard (+/+) minks. Conversely, the homozigosity for two coat color loci in double recessive pearl minks (k/k p/p) significantly decreases the noradrenaline and serotonin contents of the hypothalamus. In addition, monorecessive and double recessive minks differ from each other in the serotonin contents of the midbrain and medulla.

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.

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.