Antagonism of caffeine induced behavioral and neurochemical responses by diazepam

Caffeine injected at doses of 80mg/kg i. p; elicited a specific rotatory behaviour in rats, which was antagonized by low [1mg/kg] doses of diazepam. Decreases of openfield locomotion were not antagonized by diazepam. Caffeine administration resulted in an increase of tryptophan concentration in the hippocampus, cortex and brain stem, but decreased it in the hypothalamus and striatum. Diazepam administration also increased tryptophan levels in the hippocampus, brain stem and striatum; but decreased it in the cortex and hypothalamus. Caffeine plus diazepam co - administration normalized tryptophan levels only in the hippocampus and cortex. A role of hippocampal and cortical serotonin in caffeine - induced anxiety and anti - anxiety effects of diazepam is discussed

Greater enhancement of central serotonin metabolism by a tryptophan load in ethanol injected rats

Previously, long-term treatment with ethanol has been shown to enhance rat brain 5-hydroxytryptamine [5-HT] metabolism. A possible increase in the activity of the regulatory enzyme tryptophan hydroxylase was suggested because brain or plasma concentrations of tryptophan were not altered. Tryptophan injection [50 mg/kg] increased brain but not plasma tryptophan concentration more in long term ethanol treated rats. In the present study, 2 h. after ethanol injection [25% v/v; 3 ml/kg] hepatic apo-tryptophan pyrrolase activity was increased in rats. But due to slight decrease in the activity of holoenzyme, changes in the total enzyme activity were not significant. Plasma concentrations of total and free tryptophan and brain tryptophan were also not altered. But 5-HT and 5-hydroxyindoleacetic acid [5-HIAA] levels increased in the brain, again suggesting a possible increase in the activity of tryptophan hydroxylase. The effect of a tryptophan load on brain 5-HT metabolism was therefore compared in previously ethanol or saline injected rats. One h. after tryptophan [50 mg/kg i.p] injection plasma concentrations of tryptophan were only 16.5% greater in previously ethanol injected rats than in saline injected animals; but brain tryptophan was 66.5% higher in the former group. Increase of 5-HT and 5-HIAA were also greater in the ethanol injected rats. The results are consistent with acute ethanol administration also enhancing serotonin metabolism and show that brain uptake/utilization of circulating tryptophan is greater in acute ethanol administered rats and may be useful in our understanding of role and possible mechanism of tryptophan/serotonin involvement in mood regulation