Several recent reports based on microdialysis have shown that repeated injections of IFN-alpha induce reduced dopamine (DA) activity in the rodent brain, and specifically within the striatum. This mesolimbic DA system is thought to play a central role in controlling latent inhibition (LI), which refers to the phenomenon in which conditioning proceeds more slowly to an irrelevant pre-exposed (PE) stimulus. The purpose of the present experiment was to evaluate whether chronic treatment with IFN-alpha may induce similar effects on LI as other DA-depleting manipulations. Rats were injected daily, for 24 days either with 10(4)IU IFN-alpha or vehicle, while monitoring their locomotor activity in photocell cages. No changes in locomotor activity, either during the acute period after the first injection, or progressively over the chronic period were observed. LI was then evaluated in these rats with a Conditioned Taste Aversion (CTA) paradigm. Half of each group of rats were pre-exposed to the 5% sucrose Conditioned Stimulus (CS) for 30 min on three successive days before the conditioning session in which the 30 min access to the 5% sucrose solution was followed by a 0.15M injection of 127 mg/kg LiCl. Two test sessions, in which rats were given a choice between the 5% sucrose solution and water, were given 48 and 72 h after the conditioning session. The results showed moderate LI in the control group, which was considerably potentiated in the IFN-alpha group despite the absence of any change in locomotor activity. These results are interpreted as providing indirect support for the theory that suggests that LI depends on DA activity in the nucleus accumbens (NAcc).