Plasma CRH was measured in maternal plasma throughout the third trimester of pregnancy, during labor, and postpartum. CRH levels were also measured in arterial and venous umbilical cord plasma samples. In normal pregnant women, plasma CRH increased from 50 +/- 15 (+/- SEM) pg/mL at 28 weeks gestation (n = 41) to 1462 +/- 182 pg/mL at 40 weeks (n = 55) and 1680 +/- 101 pg/mL (n = 65) in labor. Women with pregnancy-induced hypertension (n = 49) had plasma CRH levels significantly elevated above this normal range. Similarly, women who subsequently went into premature labor had raised levels several weeks before the onset of labor. After delivery, plasma CRH returned to normal within 15 h. Total plasma cortisol levels varied little throughout the third trimester, but increased during labor and remained elevated 2-3 days postpartum. There was, therefore, no correlation between plasma cortisol and CRH, implying that this placental CRH is not primarily involved in the control of the maternal hypothalamo-pituitary adrenal axis during pregnancy. The concentrations of CRH in umbilical cord plasma samples were considerably lower than those in the maternal circulation and were close to those in normal nonpregnant adults.

The occurrence and nature of corticosteroid inhibition of ACTH secretion at the rat anterior pituitary gland was investigated using three experimental models: animals bearing lesions of the basal hypothalamus, and two preparations of the gland incubated in vitro; these were tissue segments and collagenase-dispersed cells. Release of ACTH in the experiments was provoked using one of three distinct stimuli: acid extracts of whole hypothalami, corticotrophin releasing activity released by serotonin from hypothalami incubated in vitro and synthetic ovine corticotrophin releasing factor. Irrespective of whether ACTH was measured directly by radioimmunoassay (in the experiments in vitro) or indirectly in terms of corticosterone production (in the lesioned animals), its stimulated release from the anterior pituitary gland was inhibited by corticosterone. Two phases of inhibition were observed; these had some of the characteristics inferred previously from experiments with intact animals and designated fast feedback and delayed feedback. However, the fast feedback demonstrable in lesioned animals did not show the rate-sensitivity shown previously in intact animals. 11-Deoxycortisol (or 11-deoxycorticosterone) and prednisolone proved to be agonists of corticosterone in provoking fast feedback in lesioned animals, whereas they had been shown respectively to act as an antagonist or to have no effect in intact rats. Several steroids were able to cause delayed feedback in lesioned rats, but beclomethasone dipropionate (shown to be an agonist of corticosterone in intact rats) proved to have no inhibitory effect at the anterior pituitary gland of lesioned animals. It is concluded that the dynamics of corticosteroid feedback mechanisms at the anterior pituitary gland, as indicated by experiments in lesioned animals, differ from those operative in the intact animals. Other work suggests that a more important site for such inhibitory mechanisms in vivo is the hypothalamus.

Acute administration of d-amphetamine (up to 8 mg/kg) or l-amphetamine (up to 12 mg/kg) in the marmoset results in a dose-dependent increase in small head movements (checking), an almost total suppression of activities including eating, grooming, playing, and social interaction, but little change in the amount of movement. Severe stereotypy is seen at high doses of both isomers. The d-isomer has approximately twice the potency of the l-isomer in increasing checking behaviour.

Acute administration of d-amphetamine in the marmoset results in a dose dependent increase in small head movements (checking), and an almost total suppression of purposeful activities and social interaction. It has little effect on locomotion and does not induce stereotyped gnawing. The GABA-agonist, muscimol, decreases checking, locomotion, activities and social interaction when given alone, but induces jerking movements at large doses. When administered in combination with amphetamine, muscimol induces persistent stereotyped gnawing. On the basis of the present findings and those of experiments in rodents it is suggested that compulsive gnawing results from overactivity in the striatal efferent pathway, while checking is probably mediated by extra-striatal sites. Since the behavioural effects of muscimol resemble those of the typical neuroleptics with the exception of the induction of gnawing, it is suggested that muscimol, though sedative, may counteract certain extrapyramidal effects of neuroleptic treatment while facilitating their other behavioural effects.

Acute administration of 4 mg/kg d-amphetamine in the marmoset results in a large increase in small head movements (checking), an almost total suppression of purposeful activities and social interaction, but little change in the amount of locomotion. Checking behaviour is blocked in a dose dependent manner by 0.03--0.18 mg/kg haloperidol but not by propranolol, aceperone or diazepam, suggesting dopaminergic mediation of this behaviour. The loss of activities and social interaction after amphetamine is not antagonized by any of the drugs used in this study. Locomotion is decreased by haloperidol, propranolol and diazepam in amphetamine treated animals and by haloperidol and aceperone in normal animals.