Abstract

In female rats, the capacity for nitric oxide (NO) production within the hypothalamus is regulated by reproductive state and by the ovarian and peptidergic hormonal pattern that simulates late pregnancy. The first series of experiments described in this thesis examined the interaction of prolactin and oxytocin in upregulating nitric oxide synthase (NOS) activity and oxytocin gene expression within the hypothalamus in steroid-primed rats. Prolactin was found to upregulate NOS and this effect was mediated by oxytocin receptor activation. In addition, increased prolactin was associated with an increase in oxytocin mRNA within both the paraventricular (PVN) and supraoptic (SON) nuclei. The second set of experiments explored the inhibitory role of NO within the hypothalamic neurohypophysial system. The results demonstrated that NO modulated the activity of neurons in discrete nuclei in the hypothalamus and that this modulation was stimulus specific and varied with reproductive state. Central oxytocin administration induced more Fos expression within the SON and PVN in lactating than in nonlactating rat; but the opposite effect was seen following urethane administration. Inhibiting NO production increased Fos induction following central oxytocin administration in lactating rats whereas in nonlactating rats NOS inhibition decreased Fos-lir following both types of stimulation. The third series of experiments investigated a role for NO in milk ejections and the regulation of established maternal behavior. Data from these studies revealed that central inhibition of NO production disrupted pup retrieval and maternal aggression on both Day 4 and Day 10 of lactation. Together the experiments described in this thesis show that prolactin and oxytocin interact to upregulate NOS within the PVN and SON. Moreover, the increase in capacity to produce NO during lactation has a restraining effect on the activation of oxytocin neurons by oxytocin. Finally, NO has also been shown to play an important role in maternal retrieval and aggression.