Serotonin (5-HT)1A receptor agonism and 5-HT7 receptor antagonism ameliorate the subchronic phencyclidine-induced deficit in executive functioning in mice

Psychopharmacology
Lakshmi RajagopalHerbert Y Meltzer

Abstract

Reversal learning (RL), a type of executive function, dependent on prefrontal cortical function, is impaired in rodents by subchronic (sc) treatment with the N-methyl-D-aspartate receptor antagonist, phencyclidine (PCP), a widely studied model of cognitive impairment in schizophrenia (CIS). The principal objective of this study was to determine the ability of serotonin (5-HT)1A partial agonism and 5-HT7 receptor antagonism to improve RL in scPCP-treated mice. Male C57BL/6J mice were trained on an operant RL (ORL) task, then received PCP, 10 mg/kg, or saline, bid, for 7 days, followed by a 7-day washout period. scPCP significantly diminished the percent correct responding, increased total incorrect trials, and total incorrect responses, in the reversal phase performance of the ORL task. Pre-treatment with the selective 5-HT1A partial agonist, tandospirone, or the selective 5-HT7 antagonist, SB269970, but not the 5-HT7 agonist, AS 19, reversed the scPCP-induced deficit in RL. Pre-treatment with atypical antipsychotic drug lurasidone, which is a 5-HT1A partial agonist and 5-HT7 antagonist, as well as a 5-HT2A and dopamine (D)2 antagonist, also reversed RL deficit in the scPCP-treated mice. Furthermore, the selective 5-HT1A antagon...Continue Reading

References

Dec 8, 2016·Behavioural Pharmacology·Alfredo Meneses
Aug 11, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Lakshmi RajagopalHerbert Y Meltzer

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Related Concepts

Study
Atypical Antipsychotic [EPC]
GBA2 wt Allele
Neurologic Manifestations
Prefrontal Cortex
Reaction Time
Schizophrenia
Cell Polarity
C57BL/6 Mouse
Serotonin 5-HT1A Receptor Antagonists

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