Impaired inhibition of conditioned responses produced by subchronic administration of phencyclidine to rats.

Several recent investigations have suggested that an important function of the frontostriatal system is inhibitory response control, and we previously reported that subchronic exposure to phencyclidine (PCP) produced deficits in inhibitory control in monkeys. The current studies were designed to examine whether subchronic administration of PCP to rats would subsequently affect the ability to inhibit conditioned responses when relationships between reward and stimuli of affective significance change. First, the effects of long-term exposure to PCP on acquisition of a novel, concurrent discrimination or reversal learning were assessed; PCP-treated rats were selectively impaired in the ability to acquire the reversal of an already-learned stimulus-reward association. Furthermore, there were no effects of PCP treatment on the learning of a novel instrumental response; however, PCP-treated rats produced more responses during extinction of instrumental responding than did control subjects. Finally, PCP-treated rats produced more responses for a conditioned reinforcer than did control rats. These data suggest that PCP-treated rats are impaired in their ability to modulate behavior based upon new or changing information about stimulus-reward associations, possibly due to an inability to inhibit conditioned responding towards incentive stimuli. These effects may have relevance to mental disorders involving affective impairments and impulsivity, including schizophrenia, obsessive-compulsive disorders, and drug abuse.