Intracerebroventricular injection of a nitric oxide donor attenuates Fos expression in the paraventricular and supraoptic nuclei of lactating rats.

The exact nature of how nitric oxide (NO) acts in the regulation of milk ejection during lactation is not clearly understood at the moment. In this study, we have examined the effect of drugs which spontaneously release NO (sodium nitroprusside, SNP) or inhibit the NO synthase (NOS) enzyme (Nomega-nitro-L-arginine, L-NA) on the activity of some hypothalamic and functionally associated nuclei using Fos expression as an index of neuronal activation. Lactating rats received intracerebroventricular injection of SNP, l-NA or vehicle (saline) just before they were reunited with their pups after a 12-h period of separation and allowed to suckle for 2 h. The difference in the total pup body weight before and after the period of suckling was used as a functional end-point of milk transfer. Central injection of SNP in conscious rats significantly inhibited Fos expression in the paraventricular nucleus (PVN), supraoptic nucleus (SON), periventricular and preoptic nuclei and also decreased pup body weight compared with saline- or l-NA-injected rats. Urethane-anesthetized animals, compared with their conscious counterparts, showed increased Fos expression in the PVN and SON. However, Fos expression in the PVN of the anesthetized animals was attenuated by l-NA injection compared with SNP and saline injection. Taken together with an earlier finding that SNP disrupts the milk ejection burst of oxytocinergic neurons, these observations suggest that NO may act within the neuron(s) possibly to alter the mechanism(s) regulating the periodic neuronal burst activity during lactation.