Importance of endogenous nitric oxide synthase in the rat hypothalamus andamygdala in mediating the response to capsaicin

Although capsaicin has been shown to activate certain neuronal groups in th e hypothalamus and amygdala, the neurotransmitters involved and the exact m echanism of action are not clearly understood at present. The aim of this s tudy was to examine the hypothesis that the effect of capsaicin in the rat hypothalamus and amygdala primarily involves direct activation of the endog enous nitric oxide synthase (NOS) neurons responsible for the synthesis of nitric oxide (NO). Subcutaneous capsaicin injection in male rats, compared with vehicle, caused a significant increase in Fos expression in the parave ntricular nucleus (PVN), supraoptic nucleus (SON), and medial and cortical amygdala. The expression of nicotinamide adenine dinucleotide phosphate dia phorase, a histochemical marker for NOS, was also increased in these brain areas in addition to the periventricular and lateral hypothalamic area and central amygdaloid nucleus. Also, capsaicin significantly increased the exp ression of neuronal NOS messenger RNA and protein in the PVN, SON, and medi al amygdala as demonstrated by in situ hybridization and immunohistochemist ry, respectively. A higher proportion of the NOS neurons in the PVN, perive ntricular region, SON and amygdala showed Fos expression in response to cap saicin than vehicle injection. There was little, if any, Fos activation in the NOS-positive neurons in the lateral hypothalamic area. The capsaicin-in duced activation of the hypothalamic PVN and SON neurons and the medial amy gdaloid nucleus was attenuated in the NOS inhibitor N-omega-nitro-L-arginin e methyl ester (L-NAME) -pretreated animals in comparison with the inactive enantiomer D-NAME. These observations indicate that activation of the endo genous NOS system and production of NO constitute a major pathway through w hich capsaicin exerts its effect within the hypothalamus and amygdala. J. C omp. Neurol. 423:670-686, 2000. (C) 2000 Wiley-Liss, Inc.