Prolactin after repeated intravenous injections of cimetidine]

To 4 normal women a bolus of mg 400 of cimetidine was injected intravenously once an hour for three hours in succession and plasma prolactin behaviour studied. No depletion in prolactin pituitary storage was observed in all subjects. The possible usefulness of cimetidine for clinical diagnostic purposes is discussed.     

Influence of mediopreoptic stimulation on temperature regulation in rats before and after serotonin injection]

The effects of electrical stimulation of the Area praceoptica medialis (APM) and intraventricular serotonine injection were investigated in thirty Wistar rats tested under normo-, hypo- and hyperthermic conditions. Temperature responses such as oxygen consumption and rectal temperature were measured and heat loss was calculated. The effects of the first stimulation before serotonine injection were compared with those of the second one after serotonine application in order to prove the influence of serotonine on temperature responses due to APM stimulation. On the other hand, the influence of stimulation on changes produced by serotonine injection should be shown by the recordings of the second serotonine responses with stimulation effects and by comparison of these with those of the first serotonine responses without stimulation effects. The first APM stimulation depending on the rectal temperature before stimulation resulted in decreasing oxygen consumption in hypothermic rats while increasing that of hyperthermic animals. There was a little decrease of rectal temperature under hyper- and normothermic conditions. while under hypothermic conditions animals showed marked depression. The increase in heat loss, however, was least in hyperthermic rats and most pronounced in hypothermic animals. The second APM stimulation did almost not affect the temperature responses after serotonine application in normothermic rats, while causing supercooling agin under hypothermic conditions and insignificant cooling at hyperthermic environment temperature. Comparison of the first and second stimulation effects revealed statistical significant differences at normo-, hypo- and hyperthermic temperatures. The results are discussed under consideration of the different starting conditions before the first and second stimulation. These findings do not indicate that serotonine would shift the sensibility of mediopraeoptic structures and thus unequivocally modifies stimulation effects.     

Role of proto-oncogenes in the regulation of proenkephalin mRNA expression induced by repeated nicotine injections in rat adrenal medulla

We have studied the effect of repeated systemic administrations of nicotine (3 mg/kg) at 30 min intervals on proenkephalin (proENK) mRNA level in rat adrenal gland. Northern blot analysis has shown that proENK mRNA expression was enhanced by repeated nicotine administrations. Additionally, repeated administrations of nicotine transiently induced the c-fos and c-jun mRNA levels after the first-third nicotine administration, and the c-fos and c-jun mRNA levels were returned to the basal level after the seventh administration of nicotine. c-Fos, c-Jun and Fra-2 protein levels were persistently increased until the seventh administration. The repeated nicotine administrations also elevated phospho-CREB without altering total CREB level in all tested groups. Immunohistochemical analysis showed that the increase of c-Fos and c-Jun proteins by repeated nicotine administrations is mostly medulla specific, while Fra-2 immuno reactivity was shown both in medulla and cortex. The repeated nicotine administrations enhanced the AP-1 and ENKCRE-2 DNA binding activities. Furthermore, the cross-competition studies revealed that the AP-1 proteins, rather than CREB, actively bind to ENKCRE-2 DNA domain. These results suggest that proENK mRNA expression induced by repeated nicotine administrations may be mediated by AP-1 proteins, such as c-Fos, c-Jun and Fra-2 rather than CREB via interacting to the ENKCRE-2 DNA binding domain in rat adrenal medulla.     

Body temperature regulation in the rat

In loosely-restrained adult conscious rats exposed to stepwise changes in ambient temperature (T(a)) from 25 to 5 degrees C or from 20 to 35 degrees C, we have recorded body and tail temperatures, metabolic rate (VO(2)), shivering and ventilation (V). It was found that VO(2) and V vary with T(a) and show a nadir for a T(a) of 30 degrees C whereas shivering starts at 20 degrees C and increases progressively with cold exposure. T(tail) follows changes in T(a) whereas T(body) decreases slightly in cold and increases markedly in warm exposure. These results suggest that the control of T(body) interacts with the control of breathing in order to increase VO(2) during cold exposure and to facilitate evaporative respiratory heat dissipation during warm exposure.     

Desensitization to PAF-induced rat paw oedema by repeated intraplantar injections

The intraplantar injection of PAF-acether (PAF), induced acute oedema in the rat paw, and desensitized it to subsequent challenges with the same agonist, but not to serotonin. The desensitization was maximal (up to 80% of initial response) after seven consecutive daily injections. In this condition, PAF-induced oedema of the contralateral paw was maintained. The analogue 2-methyl carbamate-PAF (2MC-PAF) was more effective than PAF as a desensitizing agent. Furthermore, the PAF-desensitized paw was refractory to challenges with 2-MC and vice-versa. PAF-acether, but not serotonin-induced rat paw oedema was inhibited by previous intravenous injection of PAF. Intravenous injections of serotonin were also effective in inhibiting selectively serotonin-induced paw oedema, but it was not possible to induce desensitization by repeated intraplantar injections of serotonin. Desensitization to PAF or the pre-treatment with the PAF antagonist BN 52021 did not block the edematogenic response induced by carrageenan.     

Effect of serotonin on smooth muscle]

Serotonin caused contracion of the smooth muscles of the deferent duct and of the strip of rat stomach, acting upon the D-serotonin receptors. Only a small portion of its contractile effect (about 10--14%) was caused by the release of endogenous catecholamines. The action of serotonin on the strip of the rat stomach was accompanied by an increase of its entrance into the cells of Ca45 and Na22 isotopes. The concentration turn of the concentration-effect curve of serotonin on the stomach strip was connected with the accumulation of sodium ions in the cells.     

Effects of repeated injections of interleukin 1beta or lipopolysaccharide on the HPA axis in the newborn rat

The hypothalamic-pituitary-adrenal (HPA) axis is stimulated during immune and inflammatory processes. Interleukin 1beta (IL-1beta) and lipopolysaccharide (LPS) are known to be potent stimulators of this axis. During postnatal development, the rat seems to be hyporesponsive to many stimuli. The effects of repeated systemic injections of IL-1beta and LPS on the HPA axis were investigated in neonatal rats. IL-1beta (0.02 microg/pup, administered twice daily from postnatal day 1 to 4) induced marked elevation in plasma corticosterone (CORT) level as compared to controls and LPS groups (0.4 microg or 1.2 microg LPS/pup, injected once daily from postnatal day 1 to 4). Adrenal wet weight was significantly higher, thymus weight was significantly lower. In contrast to the organ weights, there were no differences in CORT concentrations between LPS-exposed groups and controls. However, the weights of the adrenals in rats treated with LPS were significantly increased in a dose-dependent manner as compared to controls. The high LPS dose was associated with significantly lower thymus weights as compared to controls and 0.4 microg LPS rats. Thymus weights were significantly lower following IL-1beta- than LPS-administration. It is supposed that a developing endotoxin tolerance could account for the observed absence of CORT rise after the last LPS injection.     

Change in serotonin metabolism in the rat brain in response to the repeated stimulus presentation

The content of serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5-HIAA), monoamine oxidase (MAO) activity and kinetic parameters (K(m) and Vmax) for the reaction of 5-HT deamination, were examined in various regions of the rat brain after repeated presentation of a contextual stimulus. Habituation to the stimulus was accompanied by an increase of 5-HT metabolism and active transport of 5-HIAA in the amygdala, striatum and midbrain, while these changes were not found in the prefrontal cortex and hippocampus. Kinetic studies have revealed that the enhancement of 5-HT deamination by MAO in the brain structures was mediated by different catalytic mechanisms. A significant decrease in K(m) value for 5-HT deamination in the amygdala indicated an increase in the affinity of enzyme towards 5-HT. In the striatum the enhanced MAO activity was provided by increasing maximal rate of 5-HT deamination. It is concluded that an activation of presynaptic mechanisms of the serotonergic transmission in the amygdala and striatum is involved in the inhibition of biological significance and attention to repeated presentation of stimulus.     

Effect of repeated injections of GnRH on reproductive parameters in postpartum anestrous dairy cows

To induce cyclicity in dairy cattle with prolonged postpartum anestrous, repeated dosages of gonadotrophin releasing hormone (GnRH) were administered. Twenty-one (21) Holstein dairy cows and heifers calving between October 1, 1989, and January 1, 1990, at the Louisiana State University Dairy were used in the study. The animals were defined as anestrous if their plasma progesterone remained < 1.0 ng/ml until 32 to 36 days post partum. They were randomly assigned to one of two treatment groups. Group 1 (n=6) received two injections 1 hour apart of a GnRH analogue (50 mug) (i.m.). The treatment was repeated twice weekly at 3- to 4-day intervals. Group 2 controls (n=6) received saline (1 ml, i.m.) on the same schedule as Group 1. A maximum of 12 to 13 treatments were given. Cattle that had plasma progesterone >1.0 ng/ml by 32 to 36 days post partum were identified as Group 3, or cyclic contemporaries (n=9). Postpartum anestrous in the herd was 46.2% (18 39 ). Cows in Group 1 had significantly fewer days to first plasma progesterone > 1.0 ng/ml than those in Group 2 (P < 0.05), but more days than Group 3. Cows in Group 1 also had significantly fewer treatments to induce plasma progesterone > 1.0 ng/ml than those in Group 2 (P < 0.05). There were no significant differences among treatment groups in the number of days from calving to first observed estrus or the number of days open (P > 0.05).     

The effect of 4-methyl-histamine on temperature regulation in the rat

1. 1. The histamine H₂-antagonist, 4-methyl-histamine causes a fall in body temperature when injected into the third ventricle of the rat.

2. 2. The hypothermia is prevented by prior intraventricular injection of an H₂-antagonist, metiamide, but not by an H₁-antagonist, pyrilamine.

3. 3. The fall in temperature is accompanied by increased cutaneous heat loss.

4. 4. These data support the concept that there are H₂-receptors in the central thermoregulatory pathways of the rat.

Effect of restraint stress on rat brain serotonin

Restraint-induced stress in rats was found to enhance steady state concentrations of whole brain and hypothalamic serotonin, at 1,2 and 4 h after immobilization. The increase was maximal at 1 h and tended to decline thereafter. The rate of accumulation of rat brain serotonin, in pargyline pretreated animals, was significantly enhanced after restraint stress. Bilateral adrenalectomy and metyrapone, an endogenous corticoid synthesis inhibitor, failed to affect restraint stress (1h)-induced increase in rat brain serotonin levels. Thus restraint stress-induced autoanalgesia and potentiation of the pharmacological actions of several centrally acting drugs, in rats, are serotonin-mediated responses. The results also indicate that restraint stress-induced effects on rat brain serotonin are not dependent on endogenous corticoid activity.