The effects of chronic administration of ceronapril on the partial reinforcement extinction effect and latent inhibition in rats

Previous experiments showed that acute administration of the angiotensin converting enzyme (ACE) inhibitor, ceronapril, shares with neuroleptic drugs an ability to enhance latent inhibition (LI), which consists of retardation in conditioning to a stimulus as a consequence of its prior non-reinforced pre-exposure. Experiment 1 tested whether ceronapril would produce a neuroleptic-like effect in the partial reinforcement extinction effect (PREE) at one trial a day. The PREE refers to the increased resistance to extinction observed in animals trained on a partial reinforcement (PRF) schedule compared with those trained on a schedule of continuous reinforcement (CRF). Two groups of rats were trained to run in a straight alley. The CRF group received food reward on every trial. The PRF group was rewarded on a quasi- random 50% schedule. All animals were then tested in extinction in which no reward was given. Ceronapril at a dose of 0.05 mg/kg was administered in a 2 x 2 design, with drug or no drug in acquisition and drug or no drug in extinction. Rats receiving vehicle in acquisition showed a PREE, regardless of their drug treatment in extinction. In contrast, ceronapril administered in acquisition attenuated the PREE irrespective of drug treatment in extinction, by both increasing resistance to extinction in CRF animals and decreasing resistance to extinction in PRF animals. This pattern of results does not resemble that produced by neuroleptics. The PREE procedure necessitated repeated administration of ceronapril, whereas the previous demonstrations of neuroleptic-like enhancement of LI have been obtained with acute administration. Experiment 2 therefore tested the effects of chronic ceronapril administration on LI. Under these conditions, ceronapril abolished LI. The results are discussed in relation to the antipsychotic, anti-anxiety and cognitive-enhancing effects formerly attributed to ACE inhibitors.