title: 1-aminocyclopropanecarboxylic acid (ACPC) produces procognitive but not antipsychotic-like effects in rats.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343, Kraków, Poland, nfpopik@cyf-kr.edu.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Popik
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Holuj
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Nikiforuk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kos
authors.forename: Ramon
authors.initials: R
authors.lastname: Trullas
authors.forename: Phil
authors.initials: P
authors.lastname: Skolnick
mesh_terms: D000598:Amino Acids, Cyclic / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001288:Attention / Q000187:drug effects*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
chemical_list: D000598:Amino Acids, Cyclic; D014150:Antipsychotic Agents; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C023863:1-aminocyclopropane-1-carboxylic acid; D007649:Ketamine; D010622:Phencyclidine; D003024:Clozapine