Effect of nitric oxide synthase inhibition on fos expression in the hypothalamus of female rats following central oxytocin and systemic urethane administration.

Abstract

Three experiments were carried out to investigate the pattern of neuronal activation induced by central oxytocin administration and its modulation by nitric oxide (NO). First, we compared the induction of Fos-like immunoreactivity (lir) in the supraoptic (SON) and paraventricular (PVN) nuclei and medial preoptic area (MPOA) after central oxytocin administration between nonlactating and lactating rats. Next, we investigated whether NO modulated Fos induction following central oxytocin administration using a nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). Finally, to determine whether the effects of NOS inhibition on Fos induction would generalize to stimuli other than oxytocin, we compared Fos-lir in the SON and PVN of lactating and nonlactating rats following L-NAME and urethane administration. In the first two experiments, oxytocin (50 ng in 2 microl) or vehicle was administered into the third ventricle. L-NAME (50 mg/kg) was given by an intraperitoneal (i.p.) injection 30 min before oxytocin administration (experiment 2) or an i.p. injection of urethane (1.4 g/kg) (experiment 3). In all experiments, lactating rats were tested on day 12 or 13 postpartum and nonlactating females at least 11 days after surgery or the start of the experiment. Central oxytocin infusion induced Fos expression in the SON and PVN in lactating and nonlactating rats and in the MPOA and bed nucleus of the stria terminalis in lactating rats. Overall, lactating rats that received L-NAME and oxytocin had a greater number of cells showing Fos-lir in both the SON and PVN. Conversely, L-NAME administration reduced Fos-lir in the SON and PVN in oxytocin-stimulated nonlactating rats. In urethane-treated rats, L-NAME administration did not change Fos-lir in lactating rats but reduced Fos-lir in nonlactating rats. These data suggest that the role of NO in modulating the activity of neurones in discrete nuclei in the hypothalamus varies across reproductive state and with the stimulus presented.