Furthermore, we pretreated PC-3 cells with Ki16425 before collecting the CM

d brain areas. Strong Fos-activation was detected both in somato- and viscera-sensory cortical areas in sham-operated, and stronger in 4/6NX animals. In contrast, subcortical neurons in pain-related medullary viscerosensory nucleus or in the periaqueductal central gray did not express Fos in 4/6NX rats. Actions on limbic cortical and subcortical areas. Neurons in the major limbic cortical areas were strongly activated in both sham-operated and 4/6NX animals. In the hippocampus, no Fos-activation was seen either in the CA1-CA3 regions or in the dentate gyrus, while slight activity was observed in the ventral 21147071 subiculum of 4/6NX rats. Strong Fos-activation was seen in the olfactory tubercle. Fos Activation in the Brain after Losartan and Moxonidine Treatments in 4/6NX Rats In general, losartan or moxonidine treatments altered Fosexpression throughout the CNS and showed many similarities. Actions on central monoaminergic neurons. Losartan and moxonidine markedly reduced the enhanced Fos-activation in the LC of the 4/6NX rats. In addition, moxonidine lowered the moderate Fos-activation in noradrenaline and adrenaline neurons in the ventrolateral medulla that project to the spinal sympathetic preganglionic neurons. It also reduced Fos-activity in medullary raphe neurons that project to the spinal cord of 4/6NX rats, whereas the forebrain projecting serotonin neurons in the dorsal raphe nucleus were not activated. The fairly high numbers of Fos-positive cells in the histaminergic tuberomamillary nucleus were reduced by losartan. the 26841170 Fos-activation was moderate to high in the vasopressinexpressing LGX-818 magnocellular neurons of the supraoptic and paraventricular hypothalamic nuclei which was reduced by 4/6NX. Elevation in Fos-activity was observed in the anterior part of the hypothalamus, namely in the median preoptic antrioventral third ventricle region and in the organum vasculosum laminae terminalis of the 4/6NX rats. 4/6NX did not elicit Fos- Neural Activation in 4/6 Nephrectomized Rats Actions on brain nuclei involved in the central regulation of the fluid and electrolyte homeostasis and on brain areas where no blood-brain barrier exists. The moderate Fos- activity in supraoptic and magnocellular paraventricular nuclei was slightly elevated. Moxonidine had minor effect on supraoptic nuclei, but markedly increased Fos-activity in paraventricular nucleus. Losartan did not modulate Fos-activity in OLVT, but monoxidine reduced the activity of these neurons. It is hard to explain the excitatory action of losartan on the SFO. Both drugs failed to elicit any such effect in area postrema. Actions on “stress-related”hypothalamic areas and nuclei. In 4/6NX animals the number of Fos-positive neurons in the stress-related nuclei of the hypothalamus was much lower after losartan or moxonidine treatment than that of placebo- treated rats. Both drugs failed to act on central amygdaloid neurons. Actions on pain-related brain areas. In 4/6NX rats, both drugs strongly reduced the number of Fos-positive neurons in the somatosensory cortex. They had opposite effects on the viscerosensory cortex: losartan further activated Fos, while moxonidine reduced it. Actions on limbic cortical and subcortical areas. The 4/ 6NX-induced high number of Fos-positive cells in the investigated limbic cortical areas and the olfactory tubercle were diminished after moxonidine treatment. The response to losartan treatment was ambivalent. Some areas like the prefrontal cortex, showed fu