INDUCIBILITY OF C-FOS PROTEIN IN VISUO-MOTOR SYSTEM AND LIMBIC STRUCTURES AFTER ACUTE AND REPEATED ADMINISTRATION OF NICOTINE IN THE RAT

To identify neuroanatomical substrates affected by nicotine, we have s tudied its effects after acute and repeated administration through the c-Fos protein inducibility in various brain structures. Ninety minute s after acute nicotine (0.35 mg/kg, sc.) the number of c-Fos-like immu noreactive nuclei was consistently increased in visuo-motor structures such as the superior colliculus, the medial terminal nucleus of acces sory optic tract, and the nucleus of the optic tract. The anteroventra l and lateroposterior thalamic nuclei, connected with the retina and i nvolved in limbic processing, showed a c-fos induction. c-fos was pref erentially induced in terminal fields of neurons of the ventral tegmen tal area such as the nucleus accumbens,the central amygdala, the later al habenula, the lateral septum, as well as the cingulate, medial pref rontal, 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 protei n in visuo-motor, retino-limbic, subcortical, and cortical limbic stru ctures. Moreover, this chronic treatment produced an additional recrui tment of c-fos-positive nuclei in the cingulate cortex, the core and t he ventral shell of the nucleus accumbens. c-Fos induction after nicot ine differs from that reported after other addictive drugs in terms of pattern and chronic inducibility, indicating that different mechanism s are involved for maintaining this transcription factor. In addition to a preferential sensitivity of mesolimbic dopaminergic neurons to ni cotine, activation of visuo-limbic and limbic regions could be relevan t for understanding some context-dependent and addictive behaviors pro duced by nicotine. Synapse 29:343-354, 1998. (C) 1998 Wiley-Liss, Inc.