Changing pattern of oxytocin-induced excitation of neurons in the bed nuclei of the stria terminalis and ventrolateral septum in the peripartum period

Abstract

Oxytocin acts within the limbic system (bed nuclei of the stria terminalis and ventrolateral septum) to induce maternal behaviour and to facilitate neuroendocrine activity at specific times during the peripartum period. Studies were undertaken to determine whether the timing of these effects arises from modulation of the oxytocin-induced excitation of limbic neurons. Extracellular activity of single units was recorded on urethane-anaesthetized rats and neurons were tested for responses to intracerebroventricular injection of 1.1 ng oxytocin. In the first part, animals were recorded on days 19 and 22 of pregnancy and on days 3 and 5 of lactation. No significant differences in the basal firing rates or in the proportion of oxytocin-responsive neurons were detected, but responses by neurons on day 22 of pregnancy occurred after a significant delay (10.7±2.0 min), resulting in a smaller overall response compared to the other groups. These differences in the pattern of response were not due to changes in density of oxytocin binding in the limbic areas studied, since autoradiographic detection of oxytocin binding sites using the iodinated antagonist [ 125I]d(CH 2) 5[Tyr(Me) 2,Thr 4,Orn 8,Tyr-NH 2 9]-vasotocin showed no differences between the pregnant and postpartum animals. In the second part, parturient animals (day 22 of pregnancy) received intravenous injection of the long-acting opioid antagonist naltrexone, or unilateral knife-cut lesions to the stria terminalis, a source of inhibitory inputs (including enkephalinergic) to the bed nuclei of the stria terminalis and ventrolateral septum. Both treatments abolished the characteristic delay of oxytocin-induced excitation in non-treated animals on day 22 of pregnancy, and increased the overall excitatory response. Thus, during the peripartum period, a population of limbic neurons sensitive to oxytocin display a dynamically changing pattern of excitatory responses, apparently modulated by an endogenous opioid tone and independent of changes in oxytocin receptor expression. The attenuated neuronal response to central oxytocin seen on the day of parturition could account for the absence of a facilitatory effect of oxytocin on neuroendocrine activity at this time.