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We studied nitric oxide (NO) synthase activity and serotonin content in the diencephalon of 24 hr food deprived rats. NO synthase activity was significantly increased whereas serotonin levels together with those of tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) were reduced in food deprived rats when compared to control rats. NG-Nitro-L-arginine (L-NO Arg), an inhibitor of NO synthase, was used as a tool to study the role of NO in food deprivation. Twenty-four hr food deprived male Sprague-Dawley rats were intraperitoneally (i.p.) administered L-NO Arg (12.5, 25 and 50 mg/kg) before food presentation. Control rats received a NaCl (0.9%) solution. Food consumption was monitored 1 and 2 hr after food presentation. L-NO Arg administration produced a dose-dependent reduction in food intake. Pretreatment with metergoline (2 mg/kg) but not with ritanserin (1 mg/kg) antagonized the anorectic effect of L-NO Arg. Moreover, in the diencephalon L-NO Arg significantly reduced NO synthase activity whereas it increased serotonin levels. Our data indicate that NO might have a physiological role in the regulation of food intake and suggest that brain NO may modulate the central serotoninergic system.

Restoration of blood flow after an ischaemic event generates the formation of oxygen radicals which could augment brain damage. The authors studied the effects of different doses (50, 100, 200 mg/kg/i.p.) of a new antioxidant, IRFI-016, [2(2,3-dihydro-5-acetoxy-4,6,7-trimethylbenzofuranyl) acetic acid] on brain damage in the Mongolian gerbil induced by 5 min of bilateral carotid occlusion (BCO) followed by reperfusion. Post-ischaemic brain malondialdehyde (MDA) levels and locomotor activity at different times and delayed neuronal death of hippocampal CA1 area on the fourth day after occlusion were evaluated. During reperfusion, after BCO, enhancement of brain MDA occurs (37.5%, 62.5% and 100% at 15, 30 and 60 min of reperfusion, respectively). Brain MDA postischaemic increases were reduced at 15 min of reperfusion to 15.4% and 44.4% by IRFI-016, 100 and 200 mg/kg, respectively. After 30 min of reperfusion brain MDA was reduced to 31.25% and 53.13% by IRFI-016 100 and 200 mg/kg, respectively. Hyperactivity and delayed neuronal death of CA1 were significantly reduced in postischaemic gerbils treated with the highest doses of IRFI-016. Results indicate that pretreatment with the antioxidant IRFI-016 improves in a dose-dependent manner brain damage induced by ischaemia and reperfusion in the gerbil

The effects of G 619, a dual inhibitor of thromboxane A2 (TxA2) synthase and TxA2 receptor antagonist, on cerebral ischemia and reperfusion in the Mongolian gerbil were studied. Pretreatment with G 619 reduced the elevation in plasma thromboxane levels and brain malondialdehyde (MDA) occurred after cerebral ischemia/reperfusion. Moreover, G 619, at doses of 25 and 50 mg/kg/i.p., showed to protect gerbils from morbidity, mortality, hyperactivity and delayed neuronal death caused by bilateral carotid occlusion (BCO) followed by reperfusion. The results demonstrate that treatment with dual inhibitors of TxA2 synthase/TxA2 receptor antagonist could prevent cerebral ischemic damage

Thromboxane A, has been implicated, as an important pathophysiological mediator, in vascular dii. We tested the effects of pretreatment with different doses of G 619, a dual thromboxane synthase inhibitor and thromboxane AZ receptor antagonist that showed to have positive effects in splanchnic artery occlusion shock (1), on levels of brain malonildialdehyde (a product of lipid peroxidation), mortality and hyperactivity following stroke-brain injury in the Mongolian gerbils. Brain ischemia/reperfusion injury was induced by 5 min of bilateral occlusion of common carotid arteries, a procedure which causes hippocampal lesions in the gerbils (2). G 619 (12.5,25 and 50 mg/kg/i.p.) administered 30 min before occlusion, significantly reduced brain malondialdehyde formation, mortality and hyperactivity following global cerebral ischemia. Data suggest that G 619 might be effective in improving ischemic cerebral damage.