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.

Abstract

RATIONALE:

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.

• Authors: Pascal Goetghebeur, Rebecca Dias
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 202 Issue 1-3 Pg. 287-93 (Jan 2009) ISSN: 1432-2072 [Electronic] Germany
• PMID: 18392753 (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, Psychological (drug effects)
• Excitatory Amino Acid Antagonists
• Haloperidol (pharmacology)
• Imidazoles (pharmacology)
• Indoles (pharmacology)
• Male
• Modafinil
• Phencyclidine
• Psychomotor Performance (drug effects)
• Rats
• Risperidone (pharmacology)
• Schizophrenic Psychology