Effect of melatonin on neurobehavioral dysfunctions induced by intrauterine hypoxia in rats.

Intrauterine hypoxia associated with oxidative stress represents an important risk factor for development of neurobehavioral dysfunctions. In the present study, we investigated the potential protective effect of melatonin (MEL) on neurobehavioral dysfunctions induced by chronic intrauterine hypoxia in rats by the anticonvulsant drug phenytoin (PHT), which is known by its teratogenic potential. Pregnant female rats (Wistar/DV) were orally treated by PHT (150 mg/kg) from day 7 to 18 of gestation. MEL was dissolved in drinking water (40 microg/ml) and administered from day 0 to 19 of gestation. Neurobehavioral development of offspring was evaluated from birth up to day 90 of postnatal life. The results of the study confirmed the high behavior-teratogenic potential of PHT. Prenatal administration of PHT resulted in delayed neuromotor and reflex development, decreased exploration in the open field, abnormal "circling" and impaired performaces in water maze. Co-administration of MEL failed to have any effect on neurobehavioral dysfunctions induced by PHT treatment. Even administration of MEL alone caused developmental alterations in offspring manifested by accelerated testes descent and delayed onset of negative geotaxia and startle reflex. The results suggest to pay increased attention to MEL concerning its exogenous use during pregnancy.

Effect of repeated administration of the antioxidant stobadine on the behavior of singly-housed male mice in intraspecies conflict.

The aim of the present study was to assess the effect of repeated oral administration of stobadine (70 mg/kg) on the occurrence of selected behavioral elements during exposure to an intraspecies conflict between singly-housed and group-housed male mice. Isolation induced timidity (defensive-escape behavior without attacks) in most mice (87%). This isolation-induced timidity was reduced after stobadine treatment. In the stobadine-treated group, sociable activities (following, climbing) were also decreased. After discontinuation of the treatment (18 days), aggressive behavior tended to increase in the stobadine-treated group. The results of this study are indicative of an inhibitory effect of repeated administration of stobadine on some behavioral activities of singly-housed male mice in an intraspecies conflict.

Evaluation of long-term administration of the antioxidant stobadine on exploratory behaviour in rats of both genders.

Stobadine (STO) is a prospective neuro- and cardioprotective drug with high antioxidative properties. The aim of this study was to ascertain the effect of long-term administration of STO on exploratory behaviour and habituation processes in adult virgin female and male rats. Stobadine was administered by oral gavage in a single dose of 50 mg kg(-1) day(-1) for a total of 56 days. The animals were tested for exploratory behaviour-intensity of motor and vertical activity in an open field test in three blocks of measurements (initial screening; after 56 days of STO administration; and 28 days after the last treatment). The rate of decline of motor activity was evaluated during four consecutive days of testing (interrupted habituation). Administration of STO resulted in transient inhibition of exploratory behaviour in female rats without overtly detectable toxicity. Exploratory behaviour of males was not affected by STO treatment.

Antioxidant stobadine and neurobehavioural development of the rat offspring.

Stobadine (STO) is a potential neuro- and cardioprotective drug with high antioxidative properties. The presented study investigated the effects of oral STO administration (5, 15 and 50 mg/kg/d) during pregnancy and lactation to dams on neurobehavioural development of their offspring (body growth and maturation, sensory functions, neuromotor and reflex development, levels of activity and emotional reactivity, memory and learning processes). The results of our experiments showed that long-term administration of STO had no adverse effects on the course of pregnancy and lactation in dams and on the neurobehavioural development of offspring.

Effect of long-term administration of stobadine on exploratory behaviour and on striatal levels of dopamine and serotonin in rats and their offspring.

Stobadine (STB), a cardioprotective drug, was evaluated for its effect on the intensity and habituation of exploratory behaviour in open field testing and on the levels of striatal dopamine (DA), serotonin (5-HT) and their metabolites (3,4-dihydroxyphenylacetic acid, homovanillic acid, 5-hydroxyindole-3-acetic acid) in rats and their offspring. Dams were treated by oral gavage with STB (50 mg kg-1) for a total of 56 days from 14 days before mating to day 21 postpartum (pp). The first open field measurements of the dams were performed over 4 days at the beginning of the experiment, the second on days 21-24 pp and the third on days 49-52 pp (recovery period). Their offspring were tested on postnatal (pn) days 30-33 and 60-63. The biochemical analysis (HPLC with electrochemical detection) in the dams was performed at the same time schedule as given for the open field testing, but in their offspring only on pn day 60. Motor activity of the dams was decreased on days 21-24 pp. The increase of motor activity in female offspring was observed on pn days 30-33. Neurochemical analysis of the striatum of the dams revealed a significant increase of the levels of DA, 5-HT and 5-hydroxyindole-3-acetic acid. In male offspring the levels of DA were significantly decreased, whereas in females the levels were increased. These results suggest that maternal administration of STB resulted both in dams and their offspring in minor alterations in spontaneous behaviour components and changes in the dopaminergic and serotonergic system, but without inducing overtly detectable toxicity.

Effect of long-term administration of stobadine to rats on selective variables of spontaneous behaviour of their offspring.

The present study investigated the effect of long-term administration of the cardioprotective drug stobadine (STB) to dams on selective variables of spontaneous behaviour of their offspring in open field (horizontal and vertical activities, frequency and duration of grooming, and duration of total activity and immobility) tested on day 60 of age. The treatment of dams with STB significantly increased horizontal activity of offspring in both sexes. The other variables studied were not affected, with the exception of a significant increase in the frequency and duration of grooming and in the duration of total activity in females compared to males from STB treated dams.