Blonanserin reverses the phencyclidine (PCP)-induced impairment in novel object recognition (NOR) in rats: role of indirect 5-HT(1A) partial agonism.

Abstract

Blonanserin is an atypical antipsychotic drug (APD) which, compared to other atypical APDs, is a relatively selective serotonin (5-HT)2A and dopamine D2 antagonist. Comparing blonanserin with more broadly acting atypical APDs could be useful to test the contributions of actions at other monoamine receptors, e.g. 5-HT1A receptors, to the reversal of PCP-induced novel object recognition (NOR) deficit. In this study, we tested the effect of blonanserin alone, and in combination with 5-HT1A agents, on NOR deficit induced by subchronic treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP; 2 mg/kg), b.i.d., for 7 days. Blonanserin, 1mg/kg, but not 0.3mg/kg, improved the PCP-induced NOR deficit. However, at 1mg/kg, object exploration was diminished. Co-administration of sub-effective doses of blonanserin (0.3 mg/kg) and the 5-HT1A partial agonist, tandospirone (0.2 mg/kg), significantly reversed the NOR deficit without diminishing activity during the acquisition or retention periods. The combination of WAY100635 (0.6 mg/kg), a 5-HT1A antagonist, and blonanserin (1 mg/kg), also diminished object exploration which prevented assessment of the effect of this combination on NOR. WAY100635 (0.6 mg/kg) blocked the ameliorating effect of risperidone (0.1 mg/kg), another atypical APD with low affinity for 5-HT1A receptors, but did not impair exploration. These results suggest that blonansein and risperidone, atypical APDs which lack a direct action on 5-HT1A receptors require 5-HT1A receptor stimulation to reverse the subchronic PCP-induced NOR deficit and provide a support for clinical trial of blonanserin in combination with tandospirone to ameliorate cognitive impairment in schizophrenia and to have fewer side effects.

• Authors: M Horiguchi, H Y Meltzer
• Journal: Behavioural brain research (Behav Brain Res) Vol. 247 Pg. 158-64 (Jun 15 2013) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 23538066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Isoindoles
• Piperazines
• Piperidines
• Pyridines
• Pyrimidines
• Serotonin 5-HT1 Receptor Agonists
• Serotonin 5-HT2 Receptor Antagonists
• Receptor, Serotonin, 5-HT1A
• tandospirone
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
• blonanserin
• Phencyclidine

Topics

• Animals
• Female
• Isoindoles (pharmacology)
• Phencyclidine (pharmacology)
• Piperazines (pharmacology)
• Piperidines (pharmacology)
• Pyridines (pharmacology)
• Pyrimidines (pharmacology)
• Rats
• Rats, Long-Evans
• Receptor, Serotonin, 5-HT1A (metabolism)
• Recognition, Psychology (drug effects)
• Serotonin 5-HT1 Receptor Agonists (pharmacology)
• Serotonin 5-HT2 Receptor Antagonists (pharmacology)