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 exa mine whether subchronic administration of PCP to rats would subsequently af fect the ability to inhibit conditioned responses when relationships betwee n reward and stimuli of affective significance change. First, the effects o f long-term exposure to PCP on acquisition of a novel, concurrent discrimin ation or reversal learning were assessed; PCP-treated rats were selectively impaired in the ability to acquire the reversal of an already-learned stim ulus-reward association. Furthermore, there were no effects of PCP treatmen t on the learning of a novel instrument 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 PC P-treated rats are impaired in their ability to modulate behavior based upo n new or changing information about stimulus-reward associations, possibly due to an inability to inhibit conditioned responding towards incentive sti muli. These effects may have relevance to mental disorders involving affect ive impairments and impulsivity, including schizophrenia, obsessive-compuls ive disorders, and drug abuse. (C) 2000 American College of Neuropsychophar macology. Published by Elsevier Science Inc.