Short- and long-term cardiovascular and behavioural effects of oxytocin : mechanisms involved and influence of female steroid hormones

Sammanfattning: The aim of the present thesis was to investigate short- and long-term cardiovascular and behavioural effects of oxytocin. In addition, the influence of female steroid hormones as well as possible mechanisms behind the oxytocin induced effects were investigated. For this purpose blood pressure, heart rate, nociceptive thresholds, spontaneous motor activity, weight gain, food and water intake, responsiveness of alpha 2-adrenoreceptors and hormone plasma levels were measured in female and male rats. A single injection of oxytocin (1 mg/kg s.c.) induced a transient increase in nociceptive thresholds, plasma levels of corticosterone and ACTH, and blood pressure. The increase in blood pressure was most pronounced in female rats during proestrus and oestrus. Six hours after the oxytocin injection, a second increase in nociceptive thresholds occurred as well as a decrease in corticosterone levels. In addition, a tendency to a reduction in blood pressure was seen ten hours after the oxytocin injection. In female rats observed in an open-field arena, oxytocin (0.01-1 mg/kg s.c.) induced both anxiolytic-like and sedative effects. Oestrogens enhanced the anxiolytic-like effect, whereas progesterone enhanced the sedative effect of oxytocin. A five day treatment with oxytocin (1 mg/kg s.c. or 1 [my]g/kg i.c.v.) increased nociceptive thresholds, decreased blood pressure, corticosterone as well as gastrin, insulin and cholecystokinin (CCK) levels, changed the pattern of spontaneous motor activity and promoted weight gain in female rats with a low spontaneous growth rate. All these effects were sustained for more than a week after the end of the oxytocin treatment. The decrease in blood pressure lasted for 3 weeks in cycling female rats. The same treatment with oxytocin decreased blood pressure also in male but not in female spontaneously hypertensive rats. Furthermore, oxytocin treatment increased the responsiveness of locus coeruleus (LC) alpha 2-adrenoreceptors. The decrease in gastrin, insulin and CCK levels as well as the increase in weight gain in female rats in response to oxytocin, were blocked by an oxytocin antagonist. In contrast, the antagonist did not abolish the sustained effects on nociceptive thresholds, blood pressure or spontaneous motor activity, neither when it was administered together with oxytocin for 5 days nor when given after the effects were established. The long-lasting increase in nociceptive thresholds could temporarily be reversed by the opioid antagonist naloxone. Thus opioids might have been involved in this effect of oxytocin. The effect of the alpha 2-adrenoreceptor agonist clonidine on blood pressure and spontaneous motor activity was significantly enhanced in oxytocin pretreated rats. In addition, clonidine reversed the attenuation of plasma levels of insulin and CCK in the oxytocin treated rats to an enhancement. These findings together with the increased responsiveness of LC alpha 2-adrenoreceptors suggest that alpha 2-adrenoreceptors might have been involved in these long-term oxytocin induced effects.