Neurobiological mechanisms by which nicotine mediates different types of anxiety.

The effects of nicotine administration into the dorsal hippocampus and lateral septum provide further evidence that different neurochemical and neuroanatomical substrates control behaviour in different animal tests. Thus, in the social interaction test (a model of generalised anxiety disorder), bilateral administration of nicotine (1-4 microg) into both regions has anxiogenic effects in test conditions that generate moderate anxiety. The anxiogenic effects are mediated by a nicotine-evoked increase in 5-hydroxytryptamine (5-HT) release and are reversed by co-administration of the 5-HT(1A) receptor antagonist, N-(2-(6-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl)-cyclohex -ane carboxamide trichloride (WAY 100,635). On trial 1 in the elevated plus-maze (which models the escape components of panic disorder), nicotine is without effect when administered to the dorsal hippocampus, but has anxiogenic effects after lateral septal administration. On trial 2 in the elevated plus-maze (a model of specific phobia), nicotine (1 microg) has anxiolytic effects when administered to the dorsal hippocampus, but is ineffective (4 and 8 microg) in the lateral septum.