This study examined the effect of nitric oxide (NO) on milk transfer in rats. Pups nursed by mothers that received chronic systemic injections of sodium nitroprusside (SNP) weighed significantly less than pups of mothers treated with either saline or N omega-nitro-L-arginine (NNLA). Intracerebroventricular injection of SNP or L-arginine (L-arg) but not NNLA or saline, caused a significant reduction of milk transfer from mother to pups after a 12 h separation period. Systemic oxytocin (OT) injection reversed the effect of central injection of SNP. Furthermore, SNP and L-arg inhibited, whereas NNLA permitted the characteristic milk ejection burst of OT neurones without changing myoepithelial tissue response to systemic OT. These observations suggest that NO may be involved in the regulation of milk ejection bursts and milk transfer.
Abstract Oxytocin is released under stressful conditions and corticotrophin-releasing factor (CRF) is known to be involved in mediating general 'stress responses'. We therefore examined whether CRF neurons in the paraventricular nucleus participate in the stress-induced oxytocin release in the rat. CRF (0.02 to 2 nmol) injected into the third ventricle produced a dose-dependent rise in the plasma oxytocin concentration. The oxytocin release induced by CRF occurred without a change in blood pressure, and was not affected by dexamethasone pretreatment, which prevents adrenocorticotrophin release following CRF injection. Lesioning of the paraventricular nucleus reduced oxytocin release by immobilization stress, but did not alter the release of oxytocin in response to osmotic stimulation induced by intraperitoneal injection of hypertonic saline. Anti-CRF serum injection into the third ventricle reduced delayed oxytocin response to immobilization stress. These results are consistent with the hypothesis that CRF neurons in the paraventricular nucleus are involved in the oxytocin release during immobilization stress in the rat.
Employing rabbits with bipolar electrodes chronically implanted in several parts of the brain, the effects of some hypnotics, sedatives or tranquillizers upon paradoxical sleep were investigated through observations on the distribution of spontaneous PS episodes and through measurements of the induced PS threshold.PS ceased to appear and the PS threshold was elevated by the administration of 80mg/kg body weight of bromvaleryl urea, 0.1g/kg body weight of ethinamate, 12mg/kg body weight of pentobarbital sodium or 2mg/mg body weight of morphine sulphate. On the other hand, after the administration of 40mg/kg body weight of 2-methyl-3-o-tolyl-quinazolone (MTQ), PS threshold fell while the EEG arousal threshold rose. After the administration of 1.5mg/kg body weight of chlorpromazine 6mg/kg body weight of amitriptyline or 120mg/kg body weight of meprobamate, no change was observed on the EEG arousal threshold but the PS threshold markedly raised its level.After the administration of 2mg/kg body weight of chlordiazepoxide or 0.2 mg/kg body weight of diazepam, no effect was observed on the EEG arousal threshold while PS threshold decreased its level. The recruiting response to stimulation of the centre median nucleus of the thalamus recorded from the frontal cortex was enhanced after 0.1g/kg body weight of ethinamate and after 40mg/kg body weight of MTQ. On the other hand, 1.5mg/kg body weight of chlorpromazine and 3mg/kg body weight of chlordiazepoxide had almost no effect upon the response.The effects of pentobarbital, MTQ, chlorpromazine and chlordiazepoxide upon EEG activity in the pontine reticular formation, which was assumed to be the PS generating center by JOUVET, were investigated and it was found that pentobarbital sodium markedly depressed its activity and chlorpromazine depressed it slightly, but MTQ and chlordiazepoxide produced no change. Therefore, it may be reasonable to assume that it is not by direct action on the pontine reticular formation that these two latter drugs have a facilitatingeffect on PS.In conclusion it was elucidated that the PS generating system was independent of the diffuse activating system or the recruiting system. Furthermore it was suggested that these drugs which had an inhibitory effect in the tricarboxylic acid cycle simultaneously showed a blocking effect upon the PS appearance.
In order to determine whether oxytocin release is controlled by an osmoreceptor mechanism identical with that for vasopressin release, the plasma oxytocin concentration and plasma osmolality were measured during intraatrial infusion and after intraventricular injection of various osmotic solutions in unanesthetized rats. Intraatrial infusion of 0.6M NaCl Locke solution (LS.) or 1.2M mannitol L.S. elevated plasma oxytocin significantly, while 1.2M urea L.S. caused only a small increase and isotonic L.S. did not change in plasma oxytocin. All hypertonic solutions produced significant and similar increases in the plasma osmolality. Plasma oxytocin was positively correlated with plasma osmolality in the animals infused with hypertonic NaCl or mannitol but not in the animals infused with hypertonic urea. The injection of 2μl of 0.6M NaCl artificial cerebrospinal fluid (CSF) or 1.2M mannitol CSF into the third ventricle caused a significant increase in plasma oxytocin immediately (5min after injection) without changing plasma osmolality, while the intraventricular injection of 1.2M urea CSF or isotonic CSF produced no significant change in plasma oxytocin. These results indicate that oxytocin release is controlled by osmoreceptors rather than Na receptors, that the adequate stimulus for the osmoreceptors is one which produces cellular dehydration and that the osmoreceptors are located in the brain region which is accessible to osmotic agents from both the outside and inside of the blood-brain barrier. Since the organum vasculosum of the lamina terminalis (OVLT) lacks a blood-brain barrier and is known to be involved in osmotic control of vasopressin release, a lesion was made in the anteroventral region of the third ventricle which encompasses the OVLT and the effect of hypertonic NaCl infusion on oxytocin release was examined. No significant increase in plasma oxytocin was observed after intraatrial infusion of 0.6M NaCl L.S. in the lesioned rats. All of these findings lead to the conclusion that oxytocin release is under the control of osomoreceptors identical to those for vasopressin release.
Extracellular recordings of action potentials were made and their firing rates were determined from 345 paraventricular neurosecretory cells in ovariectomized rats with or without estrogen treatment. And the effect of anterior or posterior deafferentation of the hypothalamus on the firing rates was studied. In both non-treated and estrogen-treated rats the anterior deafferentation reduced the firing rates significantly (P less than 0.05 in the non-treated rats and P less than 0.01 in the estrogen-treated rats), while the posterior deafferentiation did not change the firing rates significantly. Comparisons between firing rates in estrogen-treated rats and those in non-treated ones revealed what neurosecretory neurones with intact afferent connections and with damaged posterior connections showed a facilitatory response to estrogen but that the neurones with damaged anterior connections failed to show the response. The frequency distribution of the firing rates in each of the experimental groups showed an exponential form. In conclusion, these findings suggest that the extrahypothalmic inputs from the rostral brain regions are important factors in the maintenance of the basal activity of the paraventricular neurosecretory cells. It is also indicated that estrogen stimulates the neurosecretory cell activity indirectly via afferent inputs from the rostral cerebral structures.
