Comparison of haloperidol, risperidone, sertindole, and modafinil to reverse an attentional set-shifting impairment following subchronic PCP administration in the rat--a back translational study.

Selective cognitive impairments, including those of executive function as assessed using the Wisconsin Card Sort Test or intradimensional-extradimensional (ID-ED) tests, are a key feature of schizophrenia but remain inadequately treated by existing therapies. Recently, however, modafinil has been shown to improve attentional set-shifting performance in patients with schizophrenia.
The present study evaluated the recently described analogous rat ID-ED attentional set-shifting task by investigating the effects of various pharmacological challenges to a phencyclidine (PCP)-induced ED shift impairment, namely, haloperidol, risperidone, sertindole, and modafinil.
Rats were subjected to a subchronic systemic administration of either saline vehicle or PCP (5 mg/kg i.p. b.i.d. for 7 days) followed by a 7-day washout period. During this period, rats were trained to dig in baited bowls for a food reward and to discriminate based on odor or digging media. In a single test session conducted the day after the washout period (day 8), rats performed a series of discriminations following acute administration of either vehicle, or haloperidol (0.1 mg/kg s.c.), or risperidone (0.2 mg/kg i.p.), or sertindole (1.25 mg/kg p.o.) or modafinil (64 mg/kg p.o.).
The subchronic PCP-induced ED deficit was ameliorated by sertindole and modafinil but not by haloperidol or risperidone.
Overall, these findings further support that the rat ID-ED test in subchronic PCP-treated rats has utility and validity as a preclinical model of the cognitive symptoms of schizophrenia and demonstrates back-translational potential.
AuthorsPascal Goetghebeur, Rebecca Dias
JournalPsychopharmacology (Psychopharmacology (Berl)) Vol. 202 Issue 1-3 Pg. 287-93 (Jan 2009) ISSN: 1432-2072 [Electronic] Germany
PMID18392753 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Antipsychotic Agents
  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Excitatory Amino Acid Antagonists
  • Imidazoles
  • Indoles
  • sertindole
  • Phencyclidine
  • Haloperidol
  • Risperidone
  • modafinil
  • Animals
  • Antipsychotic Agents (pharmacology)
  • Attention (drug effects)
  • Benzhydryl Compounds (pharmacology)
  • Central Nervous System Stimulants (pharmacology)
  • Cognition Disorders (chemically induced, drug therapy, psychology)
  • Conditioning, Operant (drug effects)
  • Discrimination (Psychology) (drug effects)
  • Excitatory Amino Acid Antagonists
  • Haloperidol (pharmacology)
  • Imidazoles (pharmacology)
  • Indoles (pharmacology)
  • Male
  • Phencyclidine
  • Psychomotor Performance (drug effects)
  • Rats
  • Risperidone (pharmacology)
  • Schizophrenic Psychology

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: