The effect of N-methyl-D-aspartate receptor antagonists on D,L-homocysteine thiolactone induced seizures in adult rats.

The aim of our study was to investigate the effects of ifenprodil and MK-801 on D,L-homocysteine thiolactone induced seizures in adult rats.Male Wistar rats were divided into following groups: 1. Saline-treated (C, n=10); 2. D,L-homocysteine thiolactone 8 mmol/kg, i.p. (H, n=7); 3. Ifenprodil 20 mg/kg i.p. (IF, n=8); 4. MK-801 0.5 mg/kg, i.p. (MK, n=8) and 5. Groups that received IF or MK 30 minutes prior to H (IFH, n=8 and MKH, n=8). Seizure behavior was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0-4. Lethality in experimental group was recorded 90 min and 24 h upon D,L-homocysteine thiolactone administration.There were no behavioral signs of seizure activity in groups C, IF and MK.Pre-treatment with MK-801 (MKH) showed tendency to reduced incidence of convulsions, latency to the first seizure onset and the severity of seizure episodes, but statistical significance was not attained comparing to the H group. However, median number of seizure episodes was significantly decreased in MKH (p<0.05), comparing to the H group. On the other hand, ifenprodil (IFH) decreased the latency to the first seizure onset and increased the median number of seizure episodes (p<0.05). The majority of seizure episodes in IFH (72.1%, p<0.05) and MKH (73.1%, p<0.05) groups was grade 2 and significantly different comparing to the H (36.0%). Our findings suggest that MK-801 has a mild anticonvulsive effect on D,L-homocysteine thiolactone induced seizures in adult rats.

Effect of acute lindane and alcohol intoxication on serum concentration of enzymes and fatty acids in rats.

This study examines possible synergistic effects of lindane and ethanol on inducing liver injury and serum fatty acid derangement in adult male Wistar rats. When administered together, ethanol and lindane-induced even more pronounced increase of alanine aminotransferase (165 +/- 10 U/L) and gamma-glutamyltranspeptidase activity (10.3 +/- 0.6 U/L) than after isolated administration of either substance. In addition, separate administration of lindane and ethanol was followed by a significant decrease of linoleic acid level in the serum (301 +/- 38 mg/L, 276 +/- 35 mg/L vs. 416 +/- 48 mg/L). However, when ethanol administration was followed by lindane injection, serum linoleic acid was at the similar level found in the control group (516 +/- 62 mg/L). Ethanol-treated rats that received lindane 30 min after ethanol administration have shown a marked increase of palmitic (421 +/- 27 mg/L) and linolic acid level (43 +/- 5 mg/L) in comparison with rats that have been treated only with ethanol (316+/-26 mg/L for palmitic and 32 +/- 2 mg/L for linolic acid) or lindane (295 +/- 26 mg/L for palmitic and 301 +/- 38 mg/L for linolic acid). Linolic acid level was significantly greater in comparison with control group (29 +/- 1 mg/L). In conclusion, this study found enough evidence to support the hypothesis that acute ethanol intoxication potentiates lindane-induced liver injury and enhances lipid derangement.

Ethanol suppressed seizures in lindane-treated rats. Electroencephalographic and behavioral studies.

This study examines the effects of ethanol on lindane-induced seizures in rats. The animals were divided into following groups: 1. saline, 2. DMSO (dimethylsulfoxide), 3. lindane dissolved in DMSO in the dose of 4, 6 or 8 mg/kg (L(4), L(6) and L(8) groups, respectively), 4. ethanol 2 g/kg administered 30 min prior to lindane (protected groups AL(4), AL(6) and AL(8)) and 5. ethanol alone (2 g/kg). In order to determine ethanol concentration in plasma, blood samples were collected by cardiac puncture 30 and 60 min after ethanol injection. For EEG and power spectra recordings, electrodes were implanted into the skull. The lindane treatment resulted in a dose-dependent increase of seizure incidence and severity. The rats displayed severe seizure patterns characterized by high voltage spike-wave complexes, poly-spikes and sleep-like patterns in EEG, while the power spectra were intensively elevated in comparison to the corresponding controls. Ethanol alone led to increased EEG power spectra, which became dominant in the range of 0-4 Hz. For evaluation of anticonvulsant ethanol action we compared latency to seizure, incidence and seizure severity (scale from 0 to 4) in the examined groups. Ethanol diminished seizure incidence in AL(4) and AL(6) groups, decreased intensity of convulsions, and prolonged duration of latency period in AL(8) group. We observed suppression of the EEG signs of lindane-provoked epileptiform activity in AL(4) and AL(6), but not in AL(8) group. These results suggest that ethanol acted protectively on lindane-induced seizures and suppressed behavioral and epileptic EEG spiking activity.

The influence of selenium and neuroleptics on the rat brain nuclear regulatory mechanism in carcinogenesis.

The potential clinical benefit of the antitumor effect of selenium (Se) has recently been confirmed in tumor-bearing animals and human tumor cells in culture. In clinical medicine, the reduced incidence of cancer among schizophrenic patients was attributed to neuroleptic medication. However, there has been little information on the effect of Se, carcinogen, and neuroleptic on the brain cells. This investigation was carried out on the brains of male Wistar rats treated with inorganic Se, 9,10-dimethyl-1,2-benzanthracene, and chlorpromazine. Chromatin was prepared and purified from isolated brain cell nuclei. Various protein species (histones and nonhistone proteins), RNA, and DNA were extracted by different extraction procedures. A higher relative content of nonhistone proteins was found in the group of animals treated with Se alone, carcinogen alone, and Se plus carcinogen administered simultaneously when compared with other experimental and control groups. The ratio of nonhistone proteins and histones of < 1.0 in the group of animals treated with neuroleptic + carcinogen or with neuroleptic indicates a lower content of nonhistone proteins when compared to histones. We obtained a more pronounced susceptibility to degradation by DNase I in the group of animals treated with neuroleptic + carcinogen or with neuroleptic compared to chromatin in the animals treated with carcinogen alone. We conclude that neuroleptic increases protein synthesis, as well as chromatin susceptibility to enzymatic degradation, thus achieving an opposite effect of carcinogen.

Basal and stress induced concentrations of adrenal gland catecholamines and plasma ACTH during aging.

Basal and stress levels of catecholamines (CA) in the adrenal glands, and circulatory levels of adrenocorticotropic hormone (ACTH) were examined in female Wistar rats aged 1, 3, 10 and 24 months. Our data showed reduction in basal dopamine (DA) concentration in adrenal glands and an increase in this catecholamine in response to stress at all ages (1, 3, 10, 24 months). The greatest levels of basal norepinephrine (NE) and epinephrine (E) concentrations in the adrenal glands were noted in intact rats at the age of 24 months. On the other hand, the stress response of NE and DA had a tendency to fall, reaching basal values at the age of 10 and 24 months of age. Basal circulatory levels of ACTH showed a reduction with age. The stress response of ACTH was reduced in animals aged 10 and 24 months. Reduced basal values of adrenal DA and increased NE and E values, suggest that there is increased adrenomedullar activity at the age of 24 months. On the other hand, the reduced or even absent stress response of NE and E observed in the adrenals, in 10 and 24 months old rats, may be of interest in considering the ability of these animals for adaptation. Basal and stress values of plasma ACTH are significantly reduced with the onset of senescence in female rats.

Catecholamines in hypothalamus, ovaries and uteri of rats with precocious puberty.

The concentration of catecholamines in the hypothalamus and reproductive organs of rats with hypothalamic lesions placed on the day of birth was investigated. In an attempt to contribute to the discussion concerning the role of catecholamines in regulation of puberty, the aim of this study was to examine the content of hypothalamic, ovarian and uterine catecholamines in female rats with precocious vaginal opening. The animals were sacrificed on the day of precocious puberty, which occurred at the age of 25.71 +/- 0.98 days. The data obtained were compared with intact (pubertal) controls obtained on the day of vaginal opening (40.13 +/- 1.35 days) as well as in infantile intact controls of corresponding age of the lesioned animals. In the ovaries of both animals (i.e. lesioned and sacrificed on day of vaginal opening and the infantile controls of corresponding age), small and medium sized follicles were present. Ruptured follicles were evident only in the pubertal controls. The mass of ovaries and uteri from lesioned rats was also significantly lower than in the pubertal controls. Concentrations of norepinephrine in both ovaries and uteri on the day of vaginal opening of the animals with posterior hypothalamic lesions and of infantile controls, was significantly higher than in pubertal controls on the day of vaginal opening. Epinephrine was significantly higher in the uterine tissues of lesioned and infantile controls as compared to pubertal animals. The levels of dopamine and norepinephrine in the hypothalamus of lesioned and pubertal controls on the day of vaginal opening were significantly higher than in infantile controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The metabolism of dopamine in the blood of ruminant animals: an enzyme system to metabolize dopamine released from the mast cells in these species?

Following the i.v. administration of 3,4-dihydroxyphenylethylamine (dopamine) to sheep, 3,4-dihydroxyphenylethanol and 3,4-dihydroxyphenylacetic acid rapidly appeared in the blood. 3,4-Dihydroxyphenylethanol can be formed from dopamine by blood plasma of ruminants in vitro. It is suggested that this plasma enzyme system might serve to inactive dopamine released from mast cells in ruminant species.