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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.

AbstractRATIONALE:
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.
OBJECTIVE:
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.
MATERIALS AND METHODS:
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.).
RESULTS:
The subchronic PCP-induced ED deficit was ameliorated by sertindole and modafinil but not by haloperidol or risperidone.
CONCLUSIONS:
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
Topics
  • 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

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