Abstract
RATIONALE: In addition to the negative and positive symptoms of schizophrenia, cognitive deficits, including prefrontal cortical dysfunction, are now recognized as core features of this disorder. Compounds increasing the NMDA receptor function via the strychnine-insensitive glycine receptors have been proposed as potential antipsychotics. Depending on the ambient concentrations of glutamate and glycine, 1-aminocyclopropanecarboxylic acid (ACPC) behaves as either a partial agonist or a functional antagonist at the strychnine-insensitive glycine receptors. OBJECTIVES: We investigated the procognitive and antipsychotic-like effects of ACPC in rats treated with phencyclidine (PCP) or ketamine (KET), compounds that produce psychotic-like symptoms in humans and laboratory animals. METHODS: Cognitive effects were investigated in the novel object recognition (NOR) and attentional set-shifting tests (ASST). In addition, the effects of ACPC were investigated in PCP-induced hyperactivity, conditioned avoidance response (CAR), and prepulse inhibition (PPI) tests. The effects on attention and impulsivity were measured in the five-choice serial reaction time task (5-CSRTT). RESULTS: ACPC (200-400 mg/kg) inhibited memory fading in naive rats and like clozapine prevented PCP- and KET-induced amnesia in the NOR. In naive animals, ACPC at 400 but not 200 mg/kg enhanced cognitive flexibility in the ASST, as the animals required fewer trials to reach the criteria during the extra-dimensional phase. In contrast, ACPC did not affect PCP-induced hyperactivity, CAR, and PPI as well as attention and impulsivity in the 5-CSRTT. CONCLUSION: The present study demonstrates that ACPC enhanced both object recognition memory and cognitive flexibility dependent on the prefrontal cortex, but did not affect impulsivity nor exhibit an antipsychotic-like profile.