Central temperature effects of the transmitter amino acids.

Experiments were carried out to determine the temperature changes induced by the transmitter amino acids gamma-aminobutyric acid (GABA), taurine and glycine (representatives of the inhibitor class of amino acids), and of L-glutamic acid and L-aspartic acid (representatives of the excitatory functional class of amino acids). The amino acids were introduced directly into the preoptic anterial part of the hypothalamus (PO/AH). The experiments were made on male Wistar rats into which cannules were implanted in advance in PO/AH using a stereotaxic apparatus and coordinates of administration after König and Klippel. At ambient temperature of 22 degrees C GABA and taurine are found to cause a dose-dependent hypothermal response, L-aspartic acid and L-glutamic acid lead to dose-dependent hyperthermia, while glycine does not change the body temperature.

Studies of the thyrotropic function of the adenopituitary of the offspring of rats treated during pregnancy with dopaminergic agents.

The thyrotropic function of the adenopituitary of rats, which were the offspring of animals treated during pregnancy with L-DOPA, bromocriptine and haloperidol, was studied. The agents were administered according to a schedule between the 1st and the 20th day of gestation--orally for L-DOPA and bromocriptine, and intramuscularly for haloperidol--on 3-month old pregnant Wistar rats. The studies on the thyrotropic function of the pituitary were carried out on the offspring of male rats reaching sexual maturity at the age of three months at a temperature of 20 +/- 2 degrees C and with cold treatment for 60 min at 4 degrees C. The content of the thyrotrophic hormone (TTH) was determined radioimmunologically in the animals' serum. A statistically significant decrease of the basic and cold-stimulated TTH-content was observed in the serum of the offspring of rats treated during pregnancy with L-DOPA (200 mg/kg body mass) and an increase in the basic TTH content after prenatal treatment with haloperidol in doses of 1 mg/kg body mass. No statistically significant differences were found in the TTH-content in the two experimental setups, after prenatal application of bromocriptine in doses of 1 mg/kg. The effect of the dopaminergic agents applied prenatally on the development of the central neuro-regulatory mechanism, which play a role in the regulation of the TTH secretion, is discussed.

Effect of the body temperature upon central administration of substance P--the role of adrenalectomy and GABA-activation.

The change in the body temperature of rats when substance P (SP) is centrally administered is studied by using preimplanted cannules in the preoptic anterior part of the hypothalamus, both in norm and after adrenalectomy, as well as the change of this effect upon preliminary central administration of the GABAA-agonist muscimol. Substance P causes a rise in the temperature, which was significantly less manifested in the adrenalectomized animals. When the animals were pretreated with muscimol in a dose not affecting the temperature when applied independently, the SP-induced rise in the temperature was significantly less manifested in the nonadrenalectomized rats compared with the effect of independent SP administration to nonadrenalectomized animals, though significantly more pronounced compared with the effect of independent administration of SP to adrenalectomized rats. These results suggest the existence of an interaction between the GABA-ergic and the SP-ergic systems and the role of the suprarenal gland for the SP-induced hyperthermia.

Effect of some benzodiazepines on the secretion of thyrotropic hormone and prolactin under conditions of experimental stress.

The effects of diazepam and medazepam, administered repeatedly orally, on the secretion of thyrotropic hormone and prolactin in male sexually matured albino rats were investigated under conditions of acute cold and immobilization stress. The agents were administered for 30 days in doses of 1 and 5 mg/kg for diazepam, and 1 and 10 mg/kg for medazepam. Sixty minutes after the last injection, the animals were placed under conditions of low temperature--+4 degrees C (cold stress) and of immobilization (immobilization stress) for 60 min. The content of thyrotropic hormone (TTH) and of prolactin in the serum of the control and experimental animals was determined using radioimmunological methods. Diazepam and medazepam were found to inhibit prolactin secretion under stress, affecting TTH secretion only in high doses: 5 mg/kg diazepam and 10 mg/kg medazepam. The TTH content was reduced under conditions of cold stress. The role of GABA and of the benzodiazepine receptors in the central nervous system in the regulation of the secretion of prolactin and TTH under states of stress is discussed.

Changes in the antitumour effect of some cytostatic agents applied under conditions of morphine-induced hyperthermia.

The effect of the cytostatic agents bleomycetin, vincristine and methotrexate on the growth of the Lewis lung carcinoma was investigated under conditions of normothermia and morphine-induced hyperthermia. Morphine was administered 1, 3, 5, 7, 9 and 11 days after the tumour transplantation (in a single of 20 mg/kg), 75 min prior to the administration of bleomycetin (in a single dose of 2 mg/kg), vincristine (in a single dose of 0.3 mg/kg) and methotrexate (in a single dose of 5 mg/kg). The therapeutic effect was assessed on the 24th hour after the end of the treatment through determining the tumour growth inhibition. The administration of morphine to mice was found to be accompanied by the development of a hyperthermal reaction, with a maximum between the 90th and 120th min after the treatment, the change in the rectal temperature of the animals being of the order of 2.2 +/- 0.14 degrees C. Hyperthermia potentiates the effect of the antitumour antibiotic bleomycetin which, unlike bleomycin, does not manifest a threshold effect of interaction with the hyperthermia. Temperatures of the order of 40 degrees C are found to result in sensitization of the relatively resistant cells of the Lewis lung carcinoma to the antitumour effect of vincristine. Hyperthermia did not affect the activity of methotrexate. The analysis of the data obtained suggests that morphine-induced hyperthermia is a convenient model in mice for testing the behaviour of the cytostatic agents under conditions of increased temperature.

Effect of a new GABA-ergic substance gabalid on brain bioelectric activity of cat.

The effect of the GABA-ergic substance gabalid on the bioelectric activity of cats was studied using electrodes introduced into substantia nigra (SN), nucleus caudatus (NC), Amygdala basolateralis ( Abl ), mesencephalic reticular formation (MRF) and sensor motor cortex (Sm). Gabalid was administered i.p. in doses of 100 to 200 mg/k increased amplitude and frequency of spontaneous and evoked EEG activity in NC. Suppression of mean amplitude, driving reaction and evoked potentials was observed in Abl . Most expressive were the changes in the ECoG activity. We observed many regularly appearing bursts of high-amplitude alow "spindles" and an increase in the number of medium and high-amplitude waves.

Influence of morphine and haloperidol on the bioelectrical activity of n. raphe, n. caudatus, s. nigra and the visual cortex of cats.

The changes in the bioelectrical activity of n. raphe dorsalis (RD), s. nigra (SN), n. caudatus (NC) and the visual cortex (VC), induced by administration of morphinee, haloperidol, and morphine after pretreatment with haloperidol, were studied in acute experiments on 18 cats. Morphine caused changes in RD and NC, characteristic of increased excitability (increase in the amplitude and frequency of the spontaneous EEG-activity, improved assimilation upon light stimulation, higher amplitudes of the evoked potential). These phenomena were most marked until the 30th min, then they gradually decreased. In SN the bioelectrical activity was inhibited. After the initial changes suggesting inhibition, excitation phenomena occurred in the visual cortex after the 30th min. Haloperidol in SN caused changes characteristic of excitation, while in NC and VC--of inhibition. After pretreatment with haloperidol, morphine prevented its effects in all structures studied. The authors assume that the EEG-effects of morphin are conditioned both by its direct action on the serotoninergic neurones in RD and by the changes in the relationships between serotoninergic and dopaminergic neurones in RD, SN and NC.

Some approaches to experimental testing of drugs for immunotoxicity.

The paper deals with the experimental testing of drugs for immunotoxicity. Pharmacological substances used in the medical practice for long periods of time have been studied. The preliminary screening of drugs for possible immunotoxic effect consists of examination of its effects on the weight of lymphoid organs (spleen and thymus), on antibody production (plaque-forming cells and serum hemagglutinins), on serum levels of IgG and IgM and on serum complement (in vivo and in vitro). The toxicological appraisal of the results from this first step screening gives ground for further and more detailed studies on the substances that present interesting properties with regard to the modification of immune system.