The Brainstem Area Postrema may Not be Involved in Lithium-induced Activation of the Hypothalamic-pituitary-adrenal Axis

The brainstem area postrema (AP) has been suggested to be one potential site of lithium's action. In order to determine whether the AP, as a central action site of lithium, is involved in the hypothalamic-pituitary-adrenal (HPA) activation by lithium, we examined lithium-induced expression of inducible cAMP early repressor (ICER) gene in the adrenal gland of rat with lesion of AP. The adrenocortical ICER expression has been suggested to be a marker for the HPA axis activation. Sprague-Dawley rats with lesion or sham lesion of AP received intraperitoneal injection of 0.15 M LiCl at a dose of 12 ml/kg. One hour after the injection, rats were transcardially perfused with fixative and the adrenal glands were processed for ICER mRNA in situ hybridization. ICER mRNA levels in the adrenal cortex of sham lesion rats were significantly increased by lithium, compared to NaCl controls, and this increase was not affected by AP lesion. Our results suggest that the area postrema may not be involved in lithium's action to activate the HPA axis.

Adrenalectomy Abolishes Fasting-induced Down-regulation of NADPH-diaphorase in the Rat Paraventricular Nucleus

This study was conducted to define the molecular mechanism of fasting-induced down-regulation of neuronal nitric oxide synthase (nNOS) expression in the hypothalamic paraventricular nucleus (PVN). Rats were adrenalectomized (ADX), and then either underwent food deprivation or received varying doses of dexamethasone for 48 h. The brain tissues were processed for NADPH-diaphorase (NADPH-d) staining, a histochemical marker of nNOS enzyme activity. Both the ADX and the sham operated rats showed a significant weight loss after 48 h of food deprivation. Food deprivation decreased the number of NADPH-d containing cells in the PVN of sham rats, however, not in the ADX rats. Dexamethasone dose- dependently decreased NADPH-d cells in the PVN of ADX rats. The effect of ADX or dexamethasone was limited to the parvocellular subdivision of PVN. These results suggest that the adrenal glucocorticoids may down-regulate nNOS expression in the PVN during food deprivation.

Central N omega-nitro-L-arginine Methyl Ester Does not Influence Lithium-induced c-Fos and Conditioned Taste Aversion

LiCl at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the brain regions implicated in CTA formation. It has been reported that nitric oxide (NO) may play a role in CTA learning and LiCl increases both the synthesis and activity of NO synthase (NOS) in the brain. In this study, we examined the effect of central N omega-nitro-L- arginine methyl ester (L-NAME) on the brain c-Fos expression and CTA learning induced by lithium in rats. In the results, intracerebroventricular L-NAME given prior to lithium did not change either the lithium-induced CTA or c-Fos in the relevant brain regions. This suggests that the brain NO system may not be involved in the neuronal activation during lithium-induced CTA formation.

Subdiaphragmatic vagotomy induces NADPH diaphorase in the rat dorsal motor nucleus of the vagus

Axotomy of the vagal motor neurons by cervical vagotomy induces NADPH diaphorase staining due to increased nitric oxide synthase expression in both the rat dorsal motor nucleus and nucleus ambiguous; furthermore, cerical vagotomy leads to cell death of the dorsal motor nucleus cells. Subdiaphragmatic vagotomy axotomizes the vagal motor cells further from the brainstem than cervical vagotomy, and cuts the fibers running only to the abdominal viscera. Here we report that subdiaphragmatic vagotomy is sufficient to induce NADPH diaphorase staining in the dorsal motor nucleus but does not induce staining in the nucleus ambiguus. Because the neurons of the dorsal motor nucleus do not undergo cell death after subdiaphragmatic vagotomy and are able to re-enervate the gut, the increased nitric oxide synthase expression after distal axotomy may be related more to regeneration than degeneration.