Endogenous opioid actions and effects of environmental disturbance on parturition and oxytocin secretion in rats.

Blood samples were taken from conscious, chronically-catheterized rats during parturition for measurement of oxytocin by specific radioimmunoassay. After the birth of the 3rd pup, rats were allowed to remain in their nesting cage (undisturbed rats) or were transferred for 45 min to a glass bowl (disturbed rats); at the time of transfer, rats were given an i.v. injection of the opioid antagonist naloxone or saline vehicle. Subsequent parturition was prolonged in saline-treated disturbed rats, but not in naloxone-treated disturbed rats. Parturition was significantly hastened in naloxone-treated undisturbed rats. Naloxone injections were followed by a large rise in plasma oxytocin concentrations in disturbed and undisturbed rats. We conclude, from a statistical analysis of the relationship within experimental groups between plasma oxytocin concentration and speed of parturition, that the effects of disturbance and of naloxone upon parturition may be accounted for, at least in part, by their effects upon oxytocin release. However, the effects of disturbance on parturition may not be mediated entirely by activation of opioid pathways. Naloxone did not potentiate oxytocin release in non-pregnant rats, or on Day 1 post partum, but did potentiate oxytocin release on Day 22 of pregnancy even in rats before the onset of parturition. Endogenous opioid pathways regulating oxytocin release therefore appear to be active during late pregnancy and during parturition itself.

Stress-induced disruption of parturition in the rat may be mediated by endogenous opioids.

Plasma samples were obtained before and during parturition from conscious rats implanted chronically with a jugular cannula. Rats were either allowed to remain in their nesting cage throughout parturition, or were moved immediately following the birth of the second or third pup into an empty glass chamber. The time-course of parturition was prolonged for mother rats which were moved in mid-parturition to this unfamiliar environment. However, in rats given an i.v. injection of the opioid antagonist naloxone at the time of transfer, parturition followed a normal time-course, and plasma oxytocin levels were significantly higher than in animals injected with saline. Thus our hypothesis is that stress activates opioid pathways which delay parturition by inhibiting oxytocin release. Opioid-mediated mechanisms may similarly be responsible for some problems in human parturition.

Central opioids: a possible role in parturition?

Pregnant rats were implanted with subcutaneous minipumps to deliver either naloxone or saline. The time-course of subsequent parturition was different between the two groups: the interval between successive births was significantly shorter for the naloxone-treated rats. This supports the hypothesis that the opioid innervation of the neurohypophysis, which is known to influence oxytocin release profoundly, has a physiological role in parturition. To test the further hypothesis that this role is particularly important in a stressful environment, pregnant rats, again implanted with minipumps, were regularly transferred, at 15-min intervals beginning with the birth of the first pup, between their normal cage and the unfamiliar environment of a glass observation chamber. No difference was noted between the time-courses of parturition for the naloxone- and saline-treated groups, although the time-courses were markedly altered from those observed in rats not subjected to an unfamiliar environment. We conclude that opioid modulation of oxytocin release may play a role in 'spacing' the delivery of successive births during normal parturition.

Discharge of gonadotrophin-releasing hormone from the mediobasal part of the hypothalamus: effect of stimulation frequency and gonadal steroids.

The release of gonadotrophin-releasing hormone (Gn-RH), in response to electrical stimulation of the mediobasal part of the hypothalamus incubated in vitro, was studied in both male and female rats. In male rats significant release of Gn-RH occurred during the 10-min experimental period only when the incubated tissue was stimulated at frequencies of 10 Hz or greater. There was no release when stimulated at 5 Hz. There was also no release of hormone when the mediobasal hypothalami were incubated in a Ca2+ free medium. The amount of Gn-RH released during a 10-min incubation period increased progressively as the frequency of stimulation was raised from 10--100 Hz. During short (4-min) incubation periods the effectiveness of each stimulus pulse for Gn-RH release also increased with the frequency of stimulation. However, when stimulated for 10 min there was no increase in hormone released per stimulus pulse when frequency of stimulation was raised above 10 Hz. The amount of Gn-RH released in response to stimulation at 50 Hz was greater in male rats than in females. For the females, there was no significant difference between the amounts of Gn-RH released at dioestrus and pro-oestrus. In both male and female rats gonadectomised 4 weeks prior to hypothalamic incubation, the response to electrical stimulation at 50 Hz was reduced when compared with intact controls. Indeed, for the females there was no longer a statistically significant increase in the amount of Gn-RH in the incubation medium after 50 Hz stimulation. Ovariectomised female rats, injected twice daily for 3.5 days with 20 microgram of oestradiol benzoate released Gn-RH in response to 50 Hz stimulation in the same amounts as intact control animals. By contrast, there was no recovery of Gn-RH release to normal levels in castrated male rats similarly treated with 1.25 mg testosterone propionate.

The effects of hypothalamic temperature variation and intracarotid cooling on behavioural thermoregulation in sheep.

1. Shorn-sheep, placed in cold environments, have been trained to turn on infra-red heaters. The effect, on this thermoregulatory behaviour, of warming and cooling the hypothalamus by means of a thermode has been examined. 2. At ambient temperatures of 5, 15, 25 and 35 degrees C; cooling the anterior hypothalamus by means of a thermode, for periods of 20 min, resulted in a marked increase in the rate of using the heaters. 3. At ambient temperatures of 5 and 15 degrees C, warming the anterior hypothalamus for periods of 20 min caused a considerable reduction in the rate of using the radiant heaters. 4. At an ambient temperature of 10 degrees C, a 2 hr period of hypothalamic cooling resulted in an increase in the rate at which the heaters were used for the first 70 min, but after this the effect was reduced and the reduction coincided with a rise of deep body temperature of about 0-75 degress C. 5. At an ambient temperature of 10 degress C, a 2 hr period of hypothalamic warming resulted in a reduction in the rate of operating the heaters during the first 85 min, but after this period the use of the heaters increased and this increase coincided with a fall of about 0-75 degrees C in deep body temperature. 6. At ambient temperatures of 15, 25 and 35 degrees C, the cephalic region was cooled by intracarotid injections of cold saline for periods of 15 min. This procedure lowered hypothalamic temperature by about 1 degree C and produced increases in the rate at which the heaters were used similar to those seen when the thermode was cooled. To elicit marked increases in the rate at which the heaters were used it was not necessary to lower hypothalamic temperature outside the normal range.