Effects of tamoxifen and glutamate and glutamine levels in brain regions in repeated sleep deprivation-induced mania model in mice.

Protein kinase C inhibitor tamoxifen reduces symptoms of acute mania in bipolar patients and mania-like behaviors in animals. Memory impairment and altered levels of glutamate and glutamate/glutamine ratio have been reported in mania. Tamoxifen suppresses glutamate release which plays an important role in memory. The present study evaluated whether tamoxifen's activity participates in its antimanic efficacy in repeated sleep deprivation mania model. Mice were divided into control and 24-h sleep-deprived groups and were treated with vehicle or 1 mg/kg tamoxifen twice daily for 8 days. Sleep deprivation was repeated three times at intervals of 2 days. Square crossing and rearing were recorded as measures of locomotor activity. Memory and risk taking behavior were evaluated using novel object recognition and staircase tests, respectively. Glutamate and glutamine levels were measured in the frontal cortex and hippocampus. Behavioral tests were conducted 24 h after the second or immediately after the third sleep deprivations. Sleep deprivation increased locomotor activity and risk taking. Glutamate and glutamine levels and glutamate/glutamine ratio in the frontal cortex and hippocampus were unaffected. Locomotor hyperactivity was prevented by tamoxifen treatment. No change in the recognition index suggested lack of memory impairment in the model. These findings confirm the relevance of repeated sleep deprivation as a mania model and tamoxifen as an antimanic agent. However, future research is needed to further address lack of memory impairment in the model and lack of glutamatergic influence on the model and antimanic effect of tamoxifen.

The effects of superoxide anion generators on responses to exogenous nitric oxide and non-adrenergic, non-cholinergic nerve stimulation in rat isolated penile bulb.

The effects of the superoxide anion generators, pyrogallol and hydroquinone on relaxations induced by electrical field stimulation (70 V, 0.7 msec., 0.5-8 Hz for 5 sec.) and exogenous nitric oxide donor sodium nitroprusside, were investigated in rat penile bulb precontracted with phenylephrine (10(-4) M). Pyrogallol (10(-4) M, 3 x 10(-4) M) and hydroquinone (3 x 10(-4) M) reduced the relaxations induced by sodium nitroprusside, but had no effect on relaxations elicited by nitrergic nerve stimulation. After treatment with diethyldithiocarbamate (3 x 10(-3) M), an inhibitor of Cu/Zn superoxide dismutase, both agents reduced the relaxations induced by electrical field stimulation. Superoxide dismutase, at 300 U/ml, significantly reversed the inhibitory action of pyrogallol and hydroquinone on responses to sodium nitroprusside. This concentration of superoxide dismutase failed to reverse the inhibitory action of pyrogallol on responses to electrical field stimulation observed in the presence of diethyldithiocarbamate, while at 600 U/ml it significantly prevented the reduction in relaxations. However, even at 600 U/ml, superoxide dismutase did not alter the decrease in responses to electrical field stimulation evoked by hydroquinone in tissues pretreated with diethyldithiocarbamate. These results suggest that the nitrergic transmitter in rat penile bulb is protected against superoxide anions by endogenous Cu/Zn superoxide dismutase in a manner similar to gastric fundus and anococcygeus muscles.