Progressive ratio performance following challenge with antipsychotics, amphetamine, or NMDA antagonists in adult rats treated perinatally with phencyclidine

Abstract

Rationale: Previous research has shown that rats exposed perinatally to phencyclidine (PCP) exhibited neuroanatomical abnormalities and altered cognition. In addition to cognitive deficits, schizophrenic patients may also exhibit negative symptoms such as lack of motivation. Objectives: In this study, we used a progressive ratio ( PR) schedule of food reinforcement to assess motivation following early exposure to PCP. Methods: Male rat pups were injected SC with 10 mg/kg PCP on postnatal days (PN) 7, 9, and 11. On PN 120, they began training in a PR 5 schedule of food reinforcement. Results: Significant PCP effects on acquisition and baseline performance were not noted. After acquisition of the task, challenges with PCP, dizocilpine, amphetamine, haloperidol, and clozapine resulted in dose-dependent decreases in response rates of similar magnitudes in both groups. In rats that continued to respond at higher doses, PCP, dizocilpine, and clozapine failed to alter breakpoints. In contrast, a 5.6 mg/kg dose of amphetamine selectively increased breakpoints in PCP-treated rats, although very few rats responded at this dose. Haloperidol decreased breakpoints in most rats at non-sedating doses. Conclusions: These results suggest that a regimen of perinatal PCP administration sufficient to disrupt cognition did not alter motivation for food reinforcement, regardless of whether rats also received challenges with NMDA antagonists or antipsychotics. Interpretation of amphetamine's high dose effects on breakpoints was complicated by the failure of many rats to respond at this dose. Further research is needed to determine whether negative symptoms such as social withdrawal may be modeled within this neurodevelopmental approach to schizophrenia