Effects of nicotine and amphetamine on latent inhibition in human subjects

Latent inhibition (LI) is a phenomenon in which repeated non-reinforced exposure to a stimulus retards subsequent conditioning to that stimulus; it reflects a process whereby irrelevant stimuli become ignored, and has been the subject of study concerning attentional abnormalities in schizophrenia. Low doses of the indirect dopamine (DA) agonists, amphetamine and nicotine, disrupt LI in the rat. These drugs are believed to disrupt LI via DA release in the nucleus accumbens; LI in amphetamine- and nicotine-treated rats is reinstated by administration of the DA antagonist haloperidol. In human subjects, low doses of amphetamine abolish LI, and more recently haloperidol has been shown to potentiate LI. The present study investigated the effects of nicotine on LI in human subjects, and also attempted to replicate the abolition of LI by amphetamine. Nicotine failed to affect LI when administered either subcutaneously or by cigarette smoking. LI was, however, abolished in a group of subjects given 5 mg amphetamine 90 min before testing. Supplementary analyses of the data pooled from all three experiments showed that, in contrast to an earlier report, LI was no weaker in smokers than in nonsmokers