Effects of histamine and related compounds on thyrotropin secretion in rats

The effects of histamine (HA) and related compounds on thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) secretion in rats were studied. Histidine (1.0 g/kg), HA (5.0 mg/kg) or histamine antagonists mepyramine (MP) (100 mg/kg) or famotidine (FA) (5.0 mg/kg) were injected intraperitoneally, and the rats were decapitated at various intervals after the injection. The hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after histidine or HA injection, decreased significantly after FA injection, but was not changed by MP. The plasma ir-TRH concentration did not change significantly after injection of these drugs. The plasma TSH levels decreased significantly in a dose-related manner after histidine or HA injection and increased significantly in a dose-related manner after FA injection. The plasma thyroid hormone levels showed no changes. In the FA-pretreated group, the inhibitory effect of histidine or HA on TSH levels was prevented, but not in the MP-pretreated group. The plasma ir-TRH and TSH responses to cold were inhibited by histidine or HA and enhanced by FA. The plasma TSH response to TRH was inhibited by histidine or HA and enhanced by FA. The inactivation of TRH immunoreactivity by hypothalamus or plasma in vitro after histidine, HA, MP or FA was not different from that of the control. These findings suggest that histamine may act both on the hypothalamus and the pituitary to inhibit TRH and TSH release, and that its effects may be mediated via H2-receptor.     

The impairment of learning of conditioned avoidance response in rats after 6-hydroxydopamine.

Intraventricular injection of 250 mug of 6-hydroxydopamine, twice in two days apart caused a complete abolition of learning of conditioned avoidance response (CAR) in rats. L-DOPA in a dose of 100 mg/kg and then in a dose of 200 mg/kg 1. p. injected during several days did not restore the learning of CAR. This indicates that intact catecholaminergic neurons are essential for the learning of CAR. We suggest that different brain mechanisms are involved in learning and maintaining gross locomotor behavior.     

Different roles of dopamine and serotonin in conditioned passive avoidance response of rats

Deamination of dopamine and serotonin by monoamine oxidase was studied in the prefrontal cortex, striatum, hippocampus and amygdaloid complex of the brain of rats during retrieval of conditioned passive avoidance response. Changes in the dopamine and serotonin metabolism were observed in different brain structures. A decrease in dopamine-deaminating activity of monoamine oxidase was found in the hippocampus, striatum and prefrontal cortex. At the same time, serotonin-deaminating activity of the enzyme was decreased in the striatum and increased in the amygdaloid complex, whereas it did not change in the prefrontal cortex and hippocampus. The observed changes in dopamine metabolism in the prefrontal cortex and hippocampus and serotonin metabolism in the amygdaloid complex indicate that dopamine and serotonin are involved in the regulation of two different processes mediating the memory trace retrieval. Dopamine is involved in neuronal mechanisms of information processes providing the strategy of behavior, whereas serotonin is related to emotional mechanisms of memory.     

Vasopressin's effects on acquisition and extinction of conditioned avoidance response to smoking

Lysine-8-vasopressin (LVP) 5 I.U. or NaCl was administered intranasally daily for 5 days in a double blind study to 14 women and 7 men volunteers, 30 minutes prior to aversive conditioning sessions designed to assist them to stop smoking. Subjects were asked to record the number of urges to smoke, the strength of their strongest urge to smoke and the number of cigarettes smoked on a daily basis. Adequate data was obtained from 17 subjects for the Lead-in (pretreatment) week and for the Treatment week. Of these, 10 continued to supply sufficient responses through the sixth week of follow-up. During the week of aversive conditioning those subjects receiving LVP smoked significantly fewer cigarettes than the saline treatment group (p<0.01). During the Follow-up period the LVP group had significantly more urges to smoke than the saline group (p<0.01). The LVP group also smoked significantly more cigarettes than the saline group 4 weeks (p<0.05) and 6 weeks (0.01) after the Treatment week. LVP was associated with a facilitation of the acquisition of the avoidance response to smoking followed by an apparent acceleration of the extinction of the avoidance response compared to saline.     

Antifertility effects of some sulphonamides and related compounds and their accumulation in the epididymides of male rats

Nineteen sulphonamides and related drugs were screened for their antifertility effects in male rats. They were suspended in corn oil and fed orally to rats at 10 times the human dose for a period of 6 months. Of the 19 compounds tested, sulphamethazine, sulphapyridine, dapsone, sulphamethoxypyridazine, sulphaguanidine, sulphathizole, sulphamerazine and sulphadimethoxine reduced fecundity of male rats to 34.3, 37.6, 38.3, 53.6, 55.6, 58, 75 and 78.6% of control, respectively. The fall in fecundity was due to a reduction in the number of embryos compared with the number of corpora lutea per pregnant female, and, in some cases, was associated with a fall in epididymal sperm concentration and motility. Some of these compounds accumulated in the cauda epididymidis at concentrations equal to or higher than the free drug concentrations in the blood. It is proposed that the antifertility effects of some of these compounds may in part be mediated through a direct effect on epididymal stored spermatozoa, hence compromising some processes vital for fertilization.     

The effects of adenosine triphosphate and related compounds on some hydrodynamic properties of glycerinated cilia

Cilia were isolated from Tetrahymena pyriformis by a glycerol method. The addition of low concentrations of ATP, but not of other nucleoside triphosphates, caused an increase of up to twofold in the amount of cilia pelleted in a low-speed centrifugation assay and decreased the density of the pellets compared to control pellets. Pellet size and density depend on pH, both in the absence and in the presence of low concentrations of ATP. High concentrations (5 mM and above) of ATP and of other nucleoside triphosphates tend to "dissolve" the cilia. Heating the cilia for 11 min at 40°C abolishes the increase in pellet size and the decrease in pellet density caused by low ATP, but slightly increases the ATPase activity of the cilia. Heat treatment, however, does not prevent the dissolving effect of high ATP. There are, thus, two independent effects of ATP on the hydrodynamic properties of cilia suspensions.