Biphasic effect of L-5-HTP in the Vogel conflict model.

Abstract

The effect of L-5-HTP (25 400 mg/kg IP) following inhibition of the peripheral aromatic amino acid decarboxylase by means of benserazide (25 mg/kg IP) was investigated in a test modified from Vogel's drinking conflict model. At 50 mg/kg an anti-conflict action was detected, while higher doses (100-400 mg/kg) decreased punished responding. A lower dose (25 mg/kg) had no effect. Non-specific effects--such as alterations in muscle tone, in motivation to drink or in the sensitivity to electrical shock--could not explain the anxiolytic- and anxiogenic-like actions of 50 and 100 mg/kg, respectively. The bi-phasic effect of L-5-HTP is discussed in terms of different subpopulations of central serotoninergic receptors, possibly exerting opposing influences on conflict responding. The study emphasises the importance of 5-HT mechanisms in anxiety, and the possibility of finding novel anxiolytics among drugs selectively affecting central 5-HT neurotransmission.