In the present study we demonstrate that consumption of a tryptophan-deficient diet for a period of 14 days decreased the striatal serotonin and 5-hydroxyindolacetic acid tissue content in rats, whereas the level of dopamine remained unchanged. Under this condition of diminished serotonergic tone, a challenge dose of cocaine (10mg/kg, i.p.) significantly increased motor activity and dopamine extracellular content in the nucleus accumbens compared to rats fed with a balanced diet. We moreover found that pretreatment with cocaine (7 and 10mg/kg, i.p.) produced a significant increase in preference for a cocaine-associated environment in the tryptophan-deficient group compared to control rats. Our experiments show that a low tone of serotonergic system, augments the behavioural reinforcing effect of cocaine and that this effect may be due to a increased cocaine-induced accumbal dopamine release. These data indicate that a tryptophan-deficient diet alters the behavioural and neurochemical effect of psychostimulants, such as cocaine, and suggest an important role of serotonin in modulation of these effects.