Effects of theophylline in p-chlorophenylalanine-treated mice in a light/dark test

The effects of theophylline were examined in a light/dark test in p-chlorophenylalanine (PCPA)-treated mice to investigate serotonergic contribution to its effects. Three consecutive treatments with PCPA (200 mg/kg once daily) barely affected parameters in the light/ dark test. In vehicle- and PCPA-treated mice, theophylline (100 mg/kg) significantly decreased time spent in the light zone, which suggested its anxiogenic-like activity. In PCPA-treated mice, theophylline (50 mg/kg) also tended to decrease the time spent in the light zone. The effects of theophylline on the contents of monoamines and their metabolites in the brains of vehicle- and PCPA-treated mice were also investigated. Treatment with PCPA significantly decreased the contents of serotonin (5-HT) and its metabolite, as well as the contents of the metabolites of noradrenaline (NA) and dopamine (DA). Theophylline increased the metabolites of 5-HT, NA and DA in the brains of vehicle-treated mice. The increases produced by theophylline in the metabolites of NA and 5-HT were extinguished in PCPA-treated mice. Behavioral and biochemical data in the present study demonstrate that theophylline-induced anxiogenic-like activity was not mediated by serotonergic neuronal systems and that NAergic neuronal systems also might not contribute to the activity.