N. N. Barykina

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.

On association between cortical 5-HT2A receptors and behavior in rats with experimental thyroid disturbances.

Thyroid hormones (TH) were hypothesized to affect behavior via neurotransmission alterations. The present study was aimed to reveal effects of chronic TH deficit and excess on some types of adaptive behavior (catalepsy, acoustic startle reflex, open-field performance), sexual arousal and cerebral 5-HT2A serotonin receptors of adult Wistar rats. Administration of thyroxine synthesis inhibitor, propylthiouracil (PTU, 50 mg/l, 28 days), in drinking water produced substantial decrease in plasma thyroxine level and body weight gain, attenuated significantly acoustic startle reflex amplitude, sexual motivation and plasma testosterone surge in response to receptive female introduction, increased predisposition to catalepsy without considerable effects on open-field performance. L-thyroxine treatment (T4, 0.5 mg/l, 28 days) caused significant plasma thyroxine augmentation, somatic growth retardation and disturbances in sexual but not in other types of behavior studied. TH dysfunctions markedly increased number of DOI-induced wet dog shakes reflecting high functional activity of 5-HT2A receptors without any effect on cortical 5-HT2A receptor mRNA level. The involvement of cerebral 5-HT2A receptors alterations at posttranslational level in mechanisms of TH effects on sexual arousal was suggested. The data attract particular attention to undesirable effects of PTU and L-thyroxine treatment on 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.

Effect of chronic thyroxine treatment on catalepsy in rats

The effect of chronic thyroid hormone (thyroxine, T4) administration on the duration of cataleptic freezing was studied in males of random-bred Wistar and genetic cataleptic (GC) rat strains. It was found that thyroidectomy brought about a sharp increase in immobility time in Wistar rats. Replacement with 0.015 mg/kg per day of T4 for 30 days from the day after thyroidectomy prevented the development of predisposition to catalepsy, whereas the same dose of T4 failed to attenuate the predisposition to catalepsy in the case of a month delay between the thyroidectomy and the beginning of treatment. A chronic administration of T4 at a dose of 0.1 mg/kg per day clearly decreased the genetically determined high expression of cataleptic reaction in GC rats. The results are evidence of the involvement of T4 in the regulation of cataleptic freezing and suggest that predisposition to catalepsy may be caused or enhanced by a deficit of thyroid hormone.

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.

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.

Catalepsy and “nervousness” in rats: Results of replicated breeding

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 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.