Comparative Effect between Antidepressants and D-phenylalanine, a Phenethylamine Precursor, in an Animal Model of Depression

A relevant role has been attributed to phenethylamine in depressive disorders. It has been measured in human urine and rat brain in pathological conditions and after drug administration. Furthermore, a clinical correlation has been proposed between urinary elimination and depressive symptoms. Furthermore, its metabolic predecessor, D-phenylalanine, has been used as an antidepressant drug in the treatment of depressive disorders. The use of this amino acid has been realized alone, or in combination with classical antidepressants. In the present study, we tried to characterize its behavioural profile comparing it with imipramine and fluoxetine. Antidepressant drugs have been studied using diverse animal models. We used here the Porsolt test, or Forced Swimming Test (FST), measuring times of climbing, swimming and resting. When a comparison was performed between groups in climbing behaviour, significant differences were observed between imipramine treated group and saline controls (p < 0.05), and imipramine versus fluoxetine and D-phenylalanine (p < 0.01). When swimming was evaluated, clear differences between D-phenylalanine and the other groups were observed (p < 0.001). Additionally, a significant difference was also observed between imipramine and fluoxetine (p < 0.01). When resting was evaluated, high differences between D-phenylalanine versus all other groups were shown (p < 0.001). Observed behavioural profile was according to serotonergic antidepressant drugs effects. It is supported by the fact that swimming behaviours were increased, and a correlative decrease in resting was also present. We conclude that D-phenylalanine showed higher antidepressant potency than other classical antidepressants, at least at the doses used.