Acute Antidepressant-Like and Antianxiety-Like Effects of Tryptophan in Mice

Abstract

The antidepressant-like, antianxiety-like and sedative effects of tryptophan (TRP), in the absence and presence of p-chlorophenylalanine (p-CPA), and melatonin were studied in mice using the forced-swimming test, open-field test and activity cage, respectively. Single-dose TRP caused an antidepressant-like effect dose dependently up to 125 mg/kg. No significant effect was observed, however, when the TRP dose was increased to 250 mg/kg, i.e. a reversal of effect occurred at high dose. With p-CPA pretreatment, the effects observed at 125 and 250 mg/kg TRP were similar to those obtained at 50 and 125 mg/kg without p-CPA pretreatment, respectively. Melatonin also caused an antidepressant-like effect in a similar manner, but appeared to be less potent than TRP. These results strongly indicate that the antidepressant-like effect of TRP was due to its conversion to 5-hydroxytryptamine (5-HT). An antianxiety-like effect was observed for TRP only at 250 mg/kg dose together with p-CPA pretreatment, while no sedative effect was observed at all. In contrast, melatonin did not produce any antianxiety-like effect, but produced sedation at 200 mg/kg dose. It may be concluded that the antianxiety-like effect of TRP is unrelated to 5-HT and melatonin formation, but associated with TRP itself or, perhaps, with other anxiolytic metabolites.

Genotype-Dependent Activity of Tryptophan Hydroxylase-2 Determines the Response to Citalopram in a Mouse Model of Depression

“…Previous studies reported no effects of PCPA or the serotonergic neurotoxin 5,7-dihydroxytryptamine on immobility time in mice and rats Borsini, 1995;Redrobe et al, 1998;Page et al, 1999). Likewise, doses of TRP close to that we used had no effect on immobility time in NIH-Swiss mice, whereas at 50 -125 mg/kg TRP reduced immobility (Hilakivi-Clarke et al, 1990;Wong and Ong, 2001).…”

Conversion of L-Tryptophan into Melatonin Is the Possible Action Pathway Involved in the Effect of L-Tryptophan on Antidepressant-Related Behavior in Female Rats: Analysis of the Influence of Treatment Duration

“…Our study has the advantage of following the TRP effect over several weeks. It is consistent with the report of Wong and Ong [23], reporting an antidepresssive-like effect of a single dose of TRP in mice, such effect is dose-dependent. In the same species, the reduction of immobility by TRP in Porsolt's swim test has been also reported suggesting that TRP has antidepressant-like properties [45].…”

“…In support of this, report of Wong and Ong [23] in mice who reported that MEL caused an antidepressant-like less potent than TRP was referred, such effect was due to its conversion to 5-HT. Also, TRP supplementation provoked a significant rise in the levels of brain 5-HT in many animal species [53,64,65].…”

“…The involvement of MEL in mediating of TRP action is strongly suggested in many reports as in hypnotic function and affective and sedative action of TRP [23,27,28]. In support of this, TRP administration or a high plasma ratio between TRP and large neutral amino acids enhances brain TRP levels, and accelerates 5-HT and MEL synthesis.…”

“…Some observations show a direct association between TRP deficiency or depletion and pathological and psychiatric disorders in Humans. Thus, TRP depletion causes a rapid lowering of mood in normal males [22], induces antidepressant-like effects [23] and reverses antidepressant-induced remission [24]. It also produces depressive symptoms in remitted depressive patients [25], whereas in healthy subjects, no or only modest effects are found [26].…”