Purpose: We have modified for mice the activity wheel model of Routtenberg to study the effects of tyrosine on exercise tolerance, behavior, and brain neurochemistry.
Methods: Mice were fed for 2 h.d(-1) over a 2-wk period. During the second week, each group was injected daily with either saline or tyrosine (100 mg.kg(-1).d(-1)) and exercised on a running wheel. Controls were in cages with inactivated wheels and received the same treatment and feeding protocols as the experimental groups. Food consumption and cognitive function (eight-arm maze) were evaluated for 1 wk. Brains were then assayed for adrenergic and serotonergic metabolites.
Results: Activity together with a restricted diet caused extreme weight loss (27%) (P < 0.001) together with decreased food consumption (22%) (P < 0.001). Tyrosine restored food consumption to that of the controls (P < 0.001) with no effect on weight, since there was a 22% increase in activity (P < 0.001). Saline injections caused an 18% decrease in activity (P < 0.001). Both activity and tyrosine improved maze performance (P < 0.05). In the hypothalamus, activity caused a significant increase in 5-hydroxytryptamine (5-HT) (P < 0.001), 5-hydroxyindoleacetic acid (5-HIAA) (P < 0.01), and dopamine (P < 0.05); tyrosine prevented the increase in 5-HT (P < 0.05) and increased 5-HIAA in the controls (P < 0.01). With regard to hippocampal 5-HT, there was a significant increase in 5-HIAA following activity (P < 0.05), whereas tyrosine caused significant increase in 5-HIAA in the controls (P < 0.01). Activity significantly decreased the level of hippocampal 3,4-dihydroxyphenylacetic acid (DOPAC), whereas tyrosine decreased its level only in the controls (both at P < 0.0001). The level of tyrosine hydroxylase increased with activity (P < 0.05), and tyrosine decreased it significantly (P < 0.05).
Conclusion: Activity anorexia is associated with increased hypothalamic 5-HT concentrations. Tyrosine administration reverses this, and significantly improves food consumption, cognitive behavior, and activity performance. Such nutritional modulations may have implications for the treatment of eating disorders and, in normal circumstances, tyrosine may improve exercise tolerance and delay fatigue.