Increases in brain tryptophan concentration in stressed rats following ethanol administration

To determine the effect of acute ethanol administration on tryptophan metabolism in stressed and unstressed rats.

Phase I clinical trial.

Department of Biochemistry, University of Karachi. The investigation was carried out in the year 2004.

Male Albino Wistar rats (150-200 gm body wt) were selected and divided into four groups (n=5, in each group). Rats were injected either saline or 5% (v/v) ethanol (i.p) and were immediately subjected to 2 hours immobilization stress while respective control (non immobilized) groups remained in their home cages.

There was no effect of 2 hours immobilization stress in male rats on peripheral liver tryptophan (Tp) metabolism, but brain Tp, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) concentrations were increased by 71.6% (P<0.01), 80.4% (P<0.01) and 179% (P<0.01) respectively. Two hours immobilization stress immediately after ethanol (5% v/v, 2 ml/kg) administration in rats increases holo and total tryptophan pyrrolase enzyme activities by 276% (P<0.01) and 129% (P<0.01) in ethanol injected stressed rats when compared with ethanol injected unstressed rats. Holo enzyme was increased by 60.7% but apoenzyme was decreased by 41% in ethanol injected stressed rats when compared with similarly treated saline injected stressed rats. Liver and serum total tryptophan concentrations were decreased by 25.7% (P<0.05) and 45.6% (P<0.01) respectively. Brain Tp and 5-HIAA concentrations were increased by 176% (P<0.01) and 168% (P<0.01) respectively. In ethanol injected unstressed group of rats holo and total enzyme activities were inhibited by 65% (P<0.01) and 53.1% (P<0.01) respectively leading to increase in liver Tp concentrations by 75.4% (P<0.01). Serum total Tp concentration was decreased by 64.4% (P<0.01). Brain Tp and 5-HIAA concentrations were not effected by ethanol injected unstress rats but 5-HT concentrations were increased by 75.8% (P<0.01) when compared with saline injected unstressed rats.

It was found that increases in brain Tp concentrations were greater in ethanol injected stressed rats than in saline injected stressed group of rats when compared with their respective controls. Conditioned stress and ethanol both increase brain 5-HT concentrations when compared to saline treated unstressed controls.