title: Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats.
abstract: BACKGROUND
  Some novel antipsychotics manifest antagonistic activity at serotonin-6 receptors; however, little is known about the role of 5-HT6 receptors in ameliorating sensory gating deficits.
  
  
  OBJECTIVE
  We evaluated the effects of the combined administration of the 5-HT6 receptor antagonist SB 271046 with clozapine and haloperidol, as well as the co-administration of SB 271046 or SB 399885 with risperidone and the 5-HT2A antagonist M100907, to overcome the deficits induced by MK-801 in the prepulse inhibition (PPI) test.
  
  
  RESULTS
  MK-801 (0.1 mg/kg) produced reliable PPI deficits. Administration of SB 271046 (6 and 9 mg/kg), SB 399885 (3 and 6 mg/kg), clozapine (2.5 mg/kg), haloperidol (0.1 and 0.2 mg/kg), risperidone (0.25-1 mg/kg), and M100907 (0.5 and 1 mg/kg) did not affect the MK-801-induced deficits, but the administration of clozapine (5 mg/kg) did reverse the effects of MK-801. In MK-801-treated rats, the co-administration of inactive doses of clozapine (2.5 mg/kg) and SB 271046 (6 mg/kg) reversed the PPI impairments compared to animals that were administered inactive doses of either clozapine or SB 271046 alone. Co-administration of risperidone (1 mg/kg) or M100907 (0.5 mg/kg) with SB 271046 (6 mg/kg) or SB 399885 (3 mg/kg) also attenuated the MK-801-induced PPI deficits. In contrast, joint administration of haloperidol and SB 271046 had no effect on the PPI deficit.
  
  
  CONCLUSIONS
  The present results suggest that the 5-HT6 receptors may play adjunctive roles in antipsychotic drug action, and that the combination of 5-HT2A and 5-HT6 antagonism may represent an important element in the pharmacological profile of antipsychotic drugs.
authors: Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors: Katarzyna
authors: K
authors: Fijał
authors: Piotr
authors: P
authors: Popik
authors: Agnieszka
authors: A
authors: Nikiforuk
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005464:Fluorobenzenes / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D013216:Reflex, Startle / Q000187:drug effects*; D018967:Risperidone / Q000494:pharmacology*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D005464:Fluorobenzenes; D010879:Piperazines; D010880:Piperidines; D011985:Receptors, Serotonin; C503990:SB 399885; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013876:Thiophenes; C097216:serotonin 6 receptor; D016291:Dizocilpine Maleate; C079049:volinanserin; D003024:Clozapine; D006220:Haloperidol; C117443:SB 271046; D018967:Risperidone
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