To identify neuroanatomical substrates affected by nicotine, we have studied its effects after acute and repeated administration through the c-Fos protein inducibility in various brain structures. Ninety minutes after acute nicotine (0.35 mg/kg, sc.) the number of c-Fos-like immunoreactive nuclei was consistently increased in visuo-motor structures such as the superior colliculus, the medial terminal nucleus of accessory optic tract, and the nucleus of the optic tract. The anteroventral and lateroposterior thalamic nuclei, connected with the retina and involved in limbic processing, showed a c-Fos induction. c-Fos was preferentially induced in terminal fields of neurons of the ventral tegmental area such as the nucleus accumbens, the central amygdala, the lateral habenula, the lateral septum, as well as the cingulate, medial prefrontal, orbital and piriform cortices. In chronically treated rats (0.35 mg/kg sc., 3 x day for 14 days), the last nicotine injection given on the 15th day was still able to induce 90 minutes later c-Fos protein in visuo-motor, retino-limbic, subcortical, and cortical limbic structures. Moreover, this chronic treatment produced an additional recruitment of c-Fos-positive nuclei in the cingulate cortex, the core and the ventral shell of the nucleus accumbens. c-Fos induction after nicotine differs from that reported after other addictive drugs in terms of pattern and chronic inducibility, indicating that different mechanisms are involved for maintaining this transcription factor. In addition to a preferential sensitivity of mesolimbic dopaminergic neurons to nicotine, activation of visuo-limbic and limbic regions could be relevant for understanding some contextdependent and addictive behaviors produced by nicotine.