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Effects of serotonin depletion on behavior and neuronal oxidative stress status in rat: relevance for anxiety and affective disorders.

PURPOSE
We lesioned the hypothalamic paraventricular nucleus (PVN) of male Wistar rats using two different doses (8μg/3μl and 16μg/3μl) of 5,7-dihydroxytryptamine (5,7-DHT) and then animals were subjected to a battery of behavioral tests designed to assess anxiety and memory formation. Further, we were interested to know whether this lesion would result in neuronal oxidative stress and also if there is a correlation between the behavioral response to this lesion and brain oxidative stress.


MATERIAL/METHODS
Behavioral tests included elevated plus maze, used to assess exploration/anxiety status and radial armmaze, used for determining spatial short-term and reference memory errors. Regarding the oxidative stress, we measured the extent of some lipid peroxidation products like malondialdehyde and defense enzymes such as superoxide dismutase and glutathione peroxidase.


RESULTS
5,7-DHT lesioned rats spent more time in the open arms of the elevated maze compared to sham-operated rats, suggesting that the lesion significantly diminished anxiety-like behavior. Also, short-term memory was significantly impaired, as shown by the working memory errors in radial arm-maze task. Further analyses revealed that the 5,7-DHT lesion did not result in a significant change of reference memory errors. Regarding the oxidative stress, no significant modification of both superoxide dismutase and glutathione peroxidase specific activities from the temporal lobe were observed. However, the malondiadehyde level was significantly increased, suggesting pro-oxidant effects. Also, the linear regression between the working memory errors vs. malondiadehyde resulted in significant correlations.


CONCLUSION
5,7 DHT lesion of the PVN affects behavioral performance via interactions with systems governing novel and/or fear-evoking situations and also by increasing neuronal oxidative stress.