Effect of the 5-HT6 receptor antagonists Ro 04-6790 and Ro 65-7199 on latent inhibition and prepulse inhibition in the rat: Comparison to clozapine

Andreas Leng, Abdel Ouagazzal, Joram Feldon, Guy A. Higgins

Research output: Contribution to journalArticlepeer-review

Abstract

In the present study, we have investigated the effects of two selective 5-HT6 receptor antagonists, Ro04-6790 and Ro65-7199, in three drug-induced models of PPI disruption and on latent inhibition (LI) utilizing a conditioned lick suppression (CLS) procedure. Clozapine was included in each experiment for comparison. Neither Ro04-6790 nor Ro65-7199 (both 30 mg/kg) affected the PPI disruption produced by PCP (1.5 mg/kg sc), apomorphine (0.1 mg/kg sc), or LSD (0.1 mg/kg sc). There was also no interaction between each drug and CS preexposure in the CLS test indicating a failure of each drug to facilitate LI. In contrast, clozapine (12 mg/kg) attenuated an apomorphine and PCP-induced PPI deficit, although the PPI disruption produced by LSD was not significantly affected. At a lower dose of 5 mg/kg, clozapine also facilitated LI. Since each of these tests bear some predictive validity for the detection of antipsychotic drugs, the present studies do not support a therapeutic potential of 5-HT6 receptor antagonists in this regard.

Original languageEnglish
Pages (from-to)281-288
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume75
Issue number2
DOIs
StatePublished - May 2003
Externally publishedYes

Keywords

  • Conditioned lick suppression
  • Latent inhibition
  • Prepulse inhibition
  • Rat
  • Schizophrenia

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