Repeated injections of nicotine can produce an increase in locomotor activity and the expression of immediate-early gene, c-fos, in the central dopaminergic areas. Many studies have shown that Coptidis Rhizoma (CR) and its main alkaloid compound, berberine (BER), have a suppressive effect on the central nervous system. We examined the influence of CR or BER on repeated nicotine-induced locomotor activity in rats and the change of c-Fos expression in the brain by using immunohistochemistry. Male Sprague-Dawley rats were given CR and BER before repeated injections of nicotine hydrochloride (0.4 mg kg(-1), s.c.) twice daily for 7 days. After 3 days withdrawal, rats received a challenge injection of nicotine. Pretreatment with CR (100 mg kg(-1), i.p.) and BER (100 mg kg(-1), i.p.) significantly inhibited the nicotine-induced locomotor activity and expression of c-Fos in the striatum and the nucleus accumbens. These results suggest that CR and BER may produce inhibitory effects of nicotine on behavioural sensitization by possibly reducing postsynaptic neuronal activation in the central dopaminergic systems.