There is compelling evidence that withdrawal of neurotrophins can lead to impaired neuronal function and even apoptotic death of neurons. Recent experimental evidence suggests that antidepressant drugs and electroconvulsive treatment might work by enhancing CNS levels of neurotrophins. In addition, Lithium (LI) has been shown to exert robust neuroprotective effects apart from its well known mood-stabilizing effects in humans. In this study we investigated the effects of subchronic (14 days) treatment with various doses of LI on the NGF content of several regions of the adult rat brain. LI treatment, which resulted in prophylactic LI serum concentrations (0.72 +/- 0.08 mMol l(-1)), induced a significant (P < 0.05) increase in NGF concentrations in the frontal cortex (+23.2%), hippocampus (+72%), amygdala (+74%) and limbic forebrain (+46.7%) compared to untreated controls, whereas no effects on NGF concentrations were observed in the striatum, the hypothalamus or the midbrain, even using various LI doses. Moreover, no significant change in NGF concentrations in the frontal cortex was observed after acute (1 day) treatment with LI. Our findings lend support to the notion that an enhancement of NGF production may be specifically involved in the mechanisms of action of antibipolar treatments.