Nov 1, 2015

Nicotinic receptors and lurasidone-mediated reversal of phencyclidine-induced deficit in novel object recognition

Behavioural Brain Research
Masanori MiyauchiHerbert Y Meltzer

Abstract

Enhancement of cholinergic function via nicotinic acetylcholine (ACh) receptor (nAChR) agonism is a potential approach for the treatment of cognitive impairment associated with schizophrenia (CIAS). Some atypical antipsychotic drugs (AAPDs) enhance ACh release in rodent brain, indirectly stimulating these receptors. Here, we elucidate which nAChR subtypes mediate novel object recognition (NOR) in normal rats and contribute to the ability of the AAPD, lurasidone, to improve the NOR deficit in sub-chronic (sc) phencyclidine (PCP)-treated rats, a model for CIAS. The ability of lurasidone and nAChR ligands to reverse the scPCP-induced deficit in NOR was assessed in female, Long-Evans rats. The broad acting nAChR antagonist, mecamylamine (MEC), induced a NOR deficit in normal rats. The NOR deficit secondary to scPCP was reversed by either selective α4β2* nAChR agonism (A-85380) or α7 nAChRs agonism (PNU-282987); these effects were blocked by DHβE and MLA, selective antagonists of α4β2* and α7 nAChR, respectively. The ability of lurasidone to reverse the scPCP-induced NOR deficit was blocked by MEC, but not MLA or DHβE. However, sub-effective doses (SED) of either A-85380 or PNU-282987 potentiated the ability of SED lurasidone to rev...Continue Reading

Mentioned in this Paper

A 85380
Atypical Antipsychotic [EPC]
3-(2-azetidinylmethoxy)pyridine
Neurologic Manifestations
Mecamylamine
Schizophrenia
Chrna9 protein, rat
Phencyclidine Hydrobromide
Cholinergic Synaptic Transmission
Agon

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