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Arsenic is a well established human carcinogen and is ubiquitous in the environment. The present study demonstrates the effect of acute arsenic administration at three different doses in liver and brain of Wistar rats. Sodium arsenite was administered orally at doses of 6.3 mg/kg, 10.5 mg/kg and 12.6 mg/kg of body weight on the basis of a lethal dose 50% (LD 50 ) for 24 hr. After administration of arsenites, liver and brain were analyzed for various parameters of oxidative stress, histopathological changes and caspase-3 activity. Glutathione levels were decreased significantly in the liver at all doses. In liver the following biochemical changes were observed, a significant lipid peroxidation and cytochrome-P450 induction along with significant decrease in catalase and superoxide dismutase was observed at 10.5 mg/kg and 12.6 mg/ kg. The activity of glutathione peroxidase was increased significantly at all doses. In brain, no significant change was observed at 6.3 mg/kg. However, a significant increase in lipid peroxidation and glutathione peroxidase activity along with significant decrease in the activity of glutathione, catalase and superoxide dismutase was observed at 10.5 mg/kg and 12.6 mg/kg. The activity of glutathione-S-transferase was decreased significantly in both liver and brain at 10.5 and 12.6 mg/ kg. No significant alteration in the activity of glucose-6-phosphate dehydrogenase and glutathione reductase was observed in either liver or brain at any dose. Dose-dependent histopathological changes, observed in both liver and brain are also described. A significant increase in caspase-3 activity was observed at all doses in liver and at 10.5 and 12.6 mg/kg in brain. Sodium arsenite caused DNA cleavage into fragments and manifested as ''DNA laddering'', a hallmark of apoptosis.

The observed high incidence of smoking amongst depressed individuals has led to the hypothesis of 'self medication" with nicotine in some of these patients. The inbred Wistar-Kyoto (WKY) rats exhibit depressive-like characteristics as evidenced by exaggerated immobility in the forced swim test (FST). One aim of this study was to investigate whether nicotine may have an antidepressantlike effect in these animals. Moreover, because of human postmortem studies indicating a reduction of the hippocampus volume in depressed patients, it was of interest to determine whether such an anatomical anomaly may also be manifested in WKY rats and whether it would be affected by chronic nicotine treatment. Adult female WKY and their control Wistar rats were administered nicotine consecutively (0.2 mg/kg, ip, once or twice daily for 14 days) and their activity in an open field, as well as their immobility in FST were assessed either 15 min or 18 hr after the last injection. Another set of animals was treated twice daily with 0.2 mg/kg nicotine for 14 days and sacrificed on day 15 for stereological evaluation of the hippocampal volume. When tested 15 min after the last injection, once or twice daily nicotine exacerbated the immobility in the FST in WKY rats only. When tested 18 hr after the last injection, only twice daily nicotine treatment resulted in less immobility in the FST in WKY rats. Open field locomotor activity was not affected by any nicotine regimen. WKY rats had significantly less hippocampal volume (approximately 20%) than Wistar rats which was not altered by nicotine. These findings further validate the use of WKY rats as an animal model of human depression and signify the importance of inherent genetic differences in final behavioral outcome of nicotine.

The locus coeruleus (LC) is a dense cluster of neurons that projects axons throughout the neuroaxis and is located in the rostral pontine tegmentum extending from the level of the inferior colliculus to the motor nucleus of the trigeminal nerve. LC neurons are lost in the course of several neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. In this study, we used Nissl staining and tyrosine hydroxylase (TH) immunoreactivity to compare the human LC with that of closely related primate species, including great and lesser apes, and macaque monkeys. TH catalyzes the initial and rate-limiting step in catecholamine biosynthesis. The number of THimmunoreactive (TH-ir) neurons was estimated in each species using stereologic methods. In the LC of humans, the mean total number of TH-ir neurons was significantly higher compared to the other primates. Because the total number of TH-ir neurons in the LC was highly correlated with the species mean volume of the medulla oblongata, cerebellum, and neocortical gray matter, we conclude that much of the observed phylogenetic variation can be explained by anatomical scaling. Notably, the total number of LC neurons in humans was most closely predicted by the nonhuman allometric scaling relationship relative to medulla size, whereas the number of LC neurons in humans was considerably lower than predicted according to neocortex and cerebellum volume.