Previous data show that nicotinic receptors in the ventral tegmental area are of importance for the nicotine withdrawal syndrome. Here we have investigated the specific role of alpha7 nicotinic receptors in the ventral tegmental area for the neurobiological and behavioral consequences of nicotine withdrawal. Rats were exposed to nicotine for 14 days via s.c. osmotic minipumps. Bilateral intrategmental injections of the selective alpha7 nicotinic receptor antagonist methyllycaconitine reduced locomotion in the nicotine-treated rats, but not in control animals. Unilateral intrategmental injection of methyllycaconitine reduced dopamine output in the ipsilateral nucleus accumbens of nicotine-treated rats, but not in controls. Our results indicate that alpha7 nicotinic receptors in the ventral tegmental area are involved in the nicotine withdrawal syndrome.