K. Yu. Sarkisova

Behavioral characteristics of WAG/Rij rats susceptible and non-susceptible to audiogenic seizures.

Some rats of the WAG/Rij (Wistar Albino Glaxo from Rijswijk) and Wistar strain are susceptible for audiogenic (convulsive) seizures. In the present study, behavior of susceptible and non-susceptible rats from the WAG/Rij strain, genetically predisposed to absence epilepsy, and outbred Wistar strain, genetically not predisposed to absence epilepsy, was compared to assess the level of anxiety (in the open field, light-dark choice and elevated plus-maze tests) and the level of depression (in the sucrose consumption and forced swimming tests). Increased level of anxiety was found only in audiogenic susceptible rats both from WAG/Rij and Wistar strain, but increased level of depression was found only in WAG/Rij rats independently of their susceptibility to audiogenic seizures. The results suggest that enhanced level of depression in WAG/Rij strain rats is associated with absence epilepsy but enhanced level of anxiety with susceptibility to audiogenic seizures.

Dopamine-dependent nature of depression-like behavior in WAG/Rij rats with genetic absence epilepsy

WAG/Rij rats given placebo showed a depression-like state as compared with normal Wistar rats (lacking convulsive pathology); this was analogous to the state previously seen in rats of this line, with decreased investigative activity in the open field test, increased immobility in the forced swimming test, and decreased consumption and preference for sucrose solution (anhedonia). Chronic administration of the tricyclic antidepressant imipramine (15 mg/kg, i.p., 15 days) had therapeutic (antidepressant) effects on depression-like behavior in WAG/Rij rats. After withdrawal of antidepressant therapy, the behavior of WAG/Rij rats was not significantly different from that of Wistar rats. Acute (single-dose) administration of the selective dopamine D2/D3 receptor antagonist raclopride (100 µg/kg, i.p., 15 min before the start of behavioral testing) increased the symptoms of depression-like behavior and suppressed the antidepressant effect of chronic administration of imipramine in WAG/Rij rats. Raclopride had no significant effect on behavior in Wistar rats. Administration of the dopamine D2/D3 receptor agonist parlodel (a therapeutic form of bromocriptine) cured the depression-like behavior of WAG/Rij rats and had no significant effect on behavior in Wistar rats, with the exception of a reduction in the duration of immobility in the forced swimming test. Imipramine and raclopride had no significant effect on the levels of total movement activity and anxiety in either WAG/Rij or Wistar rats. These results demonstrate the dopamine-dependent nature of depression-like behavior in WAG/Rij rats and show the possible involvement of dopamine D2 receptors in mediating the antidepressant effect of imipramine on genetically determined depression-like behavior in WAG/Rij rats.

Prophylactic Actions of the Antioxidant Agent AEKOL on Behavioral (Psychoemotional) Disturbances Induced by Chronic Stress in Rats

The studies reported here provide the first evidence that the antioxidant preparation Aekol, which contains a mixture of vitamins A, E, and K3, has antidepressant properties and prophylactic actions in relation to behavioral (psychoemotional) disturbances induced in rats by chronic stress (neuroticization). The behavioral disturbances consisted of a state of depressivity, accompanied by increased anxiety, elimination of individual differences in behavior, and weakening of the relationships between behavioral measures, and these were recorded in the same animals in three different behavioral tests (open field test, forced swimming test, and light-dark selection test).

Effect of the (3–4) fragment of substance P on brain ischemia in rats with different types of behavior

A single administration of a fragment of substance P 30 min after ligation of the common carotid arteries increases resistance to brain ischemia primarily in rats with a passive type of behavior (improves their neurological status and prevents posthypoxic hyperactivity), prevents posthypoxic hyperactivity in rats with an intermediate type of behavior, and lowers the resistance of rats with an active type of behavior (increases their mortality and aggravates their neurological status).

Respiration and oxidative phosphorylation of the mitochondria of the brain of rats with various types of behavior

A higher level of activity of the succinate oxidase oxidative pathway was found in rats with the active type of behavior (with a high level of motoric activity and a low level of depressiveness) as compared with rats with the passive type of behavior (with a low level of motoric activity combined with low high and medium levels of depressiveness).

Depressive Behavior and Monoamine Contents in Brain Structures of Rats During Chronic Overcrowding

Effects of chronic overcrowding on the development of depressive-like behavior and changes in monoamine contents in the brain structures involved in the development of depression were studied in rats. It was shown that overcrowding increased grooming duration and did not change the number of crossed squares and postures in the open-field test. In the forced swimming test, overcrowding increased immobility time and deceased the duration of the first episode of active swimming, which attested to depressive-like behavior. Overcrowding reduced the content of dopamine in the striatum, its metabolites (homovanilic and dioxyphenylacetic acids) and dopamine metabolism rate in the hypothalamus, and increased the concentrations of norepinephrine, homovanilic acid, and dioxyphenylacetic acid in the olfactory bulb and homovanilic acid in the prefrontal cortex. No changes were found in the nucleus accumbens. Serotonin content did not change in all analyzed structures. It was hypothesized that the observed changes in the content of monoamines and their metabolites in certain brain structures could underlie the depressive-like behavior induced by overcrowding in rats.

Effect of substance P on behavior in the open field forced swimming tests in rats with various types of behavior

It was found that substance P administered to rats with active and passive types of behavior reversed their behavioral type but dit not affect the behavioral parameters of rats comprising an intermediate group. The “pure” effect of substance P (discounting the influence of repeat testing) was significant only for the number of rearings and the time of passive floating.

Pup-Associated Conditioned Place Preference Reaction and Maternal Care in Depressive WAG/Rij Rats

The acquisition of a conditioned place preference reaction (CPPR) associated with own pups and foster pups was compared in female WAG/Rij and Wistar rats, along with maternal behavior in a “place preference” chamber from day 2 to day 8 after birth. In addition, females’ behavior was assessed in the open field, elevated plus maze, and forced swimming tests before pregnancy and after birth of pups. Female WAG/Rij rats acquired the CPPR associated with their own pups (WAG/Rij) and foster pups (Wistar) less well. Thus, the number of females with increases in the time spent in the initial non-preferred sector after it was combined with pups and the number of females achieving the CPPR acquisition criterion were smaller in WAG/Rij rats than Wistar rats. Female WAG/Rij rats, as compared with female Wistar rats, showed lower levels of maternal care in the place preference chamber in relation to both their own pups and foster pups: the numbers of approaches to the pups were smaller, as were the numbers of retrievals, and the non-feeding-related times spent in contact with pups were shorter. The durations of immobility in the forced swimming test were greater in WAG/Rij females than Wistar females both before pregnancy and after delivery of pups, which is evidence for a stable depression-like state. Before pregnancy, there were no statistically significant interstrain differences in anxiety levels. After birth of pups, anxiety levels in WAG/Rij females decreased, while those in Wistar females showed no significant change. These results provide evidence that the worse acquisition of the CPPR and the decreased maternal care in depressed WAG/Rij females were not associated with the features of their own pups but were related to their depressive state. In other words, pups provided weaker reinforcement for depressed mothers than for “normal” (nondepressed) mothers.

Reversal Learning in WAG/Rij Rats with Depression-Like Behavior

Learning and reversal learning in a complex maze were studied in WAG/Rij and Wistar rats, along with behavior in an open field test, an anxiety and foot motivation test (the novelty-suppressed feeding test), and a forced swimming test. As compared with Wistar rats, WAG/Rij rats learned to perform the spatial task more slowly, performed the direct and reversal tasks more slowly, and made more errors in the complex maze. Among WAG/Rij rats, 18% failed to reach the learning criterion. In addition,WAG/Rij rats displayed fewer grooming acts in the open field test, showed longer latent periods to approaching food in a “novel” open field, ate smaller quantities of food in the home cage in the novelty-suppressed feeding test, and showed longer periods of immobility in the forced swimming test. These results provide evidence of cognitive impairments in WAG/Rij rats with depression-like behavior.

Effects of chronic injections of clebopride in low doses on behavior reactions of white rats

Effects of the selective D2 receptors antagonist clebopride on behavior of adult male rats was studied in such tests as sucrose consumption, open field, elevated plus maze, and complex maze with food reinforcement. The drug was injected in small doses (0.2 and 0.4 mg/kg) chronically within two weeks. It was shown that clebopride may have an influence on emotional and motivational state of experimental animals, on the one hand, causing depressive-like changes, and on the other hand, improving learning ability and exploratory reactions. A variety of consequences of D2 antagonist action is caused, apparently, by a competition of its post- and presynaptic effects.