Brain oxytocin receptor antagonism blunts the effects of anorexigenic treatments in rats: evidence for central oxytocin inhibition of food intake.

The inhibition of food intake in rats that results from various anorexigenic treatments is frequently associated with pituitary secretion of oxytocin (OT), but is not caused by circulating OT. We, therefore, evaluated the potential role of brain OT in mediating anorexia induced in rats by systemic administration of cholecystokinin (CCK), hypertonic saline (HS), or lithium chloride (LiCl), treatments that are known to stimulate pituitary OT secretion as well as to inhibit food intake. Food intake was analyzed in 22-h food-deprived rats pretreated with icv injections of either artificial cerebrospinal fluid (aCSF) or 9 nmol of an OT receptor antagonist, [d(CH2)5, Tyr(OMe)2,Orn8]vasotocin (OVT), which was the dose found to be most effective to antagonize the anorexia induced by CCK and HS.

Brain oxytocin receptors mediate corticotropin-releasing hormone-induced anorexia.

Central administration of corticotropin-releasing hormone (CRH) is known to inhibit food intake and stimulate pituitary oxytocin (OT) secretion in rats. These experiments addressed the possibility that the inhibition of food intake that follows central CRH administration is mediated through oxytocinergic pathways. Male food-deprived rats, with stable baseline food intakes after intracerebroventricular (icv) injections of artificial cerebrospinal fluid, received 150 pmol of CRH icv.

Oxytocin and an oxytocin agonist administered centrally decrease food intake in rats.

Intracerebroventricular administration of oxytocin (OT) and an OT agonist significantly decreased food intake in a dose-related manner in fasted rats. Central administration of an OT antagonist by itself (up to doses of 8 nmol) did not potentiate deprivation-induced food intake, but pretreatment with the OT receptor antagonist prevented the expected inhibition of food intake produced by OT and the OT agonist. Once-daily ICV injections of OT led to the development of tolerance to the inhibitory effects on food intake by the third day of treatment, but daily pretreatment with the OT antagonist prevented the development of this tolerance.

Adaptive responses to sustained volume expansion in hyponatraemic rats.

Studies were carried out to evaluate adaptive responses to water retention in an experimental model of the syndrome of inappropriate antidiuresis (SIAD). Hyponatraemia was induced by continuous s.c.

Adaptation to chronic hypoosmolality in rats.

A method for maintaining chronic severe hypoosmolality in rats is described utilizing subcutaneous infusions of the antidiuretic vasopressin analogue 1-deamino-[8-D-arginine] vasopressin (DDAVP) at rates of 1 or 5 ng/hr via osmotic minipumps in combination with self-ingestion of a concentrated, nutritionally-balanced liquid diet. Using these methods, 97.3% of all rats studied achieved stable levels of severe hyponatremia (plasma [Na+] = 111.