Apr 30, 2017

Neurochemical arguments for the use of dopamine D4 receptor stimulation to improve cognitive impairment associated with schizophrenia

Pharmacology, Biochemistry, and Behavior
Mei HuangHerbert Y Meltzer

Abstract

Dopamine (DA) D4 receptors have been implicated in schizophrenia and the ability of some atypical antipsychotic drugs (APDs) to improve the cognitive impairment associated with schizophrenia (CIAS). Systemic administration of a D4 agonist, PD168077, at a sub-effective dose, together with a sub-effective dose of lurasidone, an atypical APD which is a weak D4 receptor antagonist, reversed the deficit in novel object recognition (NOR) in rats treated subchronically with phencyclidine (PCP), a rodent model of CIAS. Atypical APDs potentially stimulate D4Rs via their ability to enhance DA release in key brain areas related to cognition. However, some atypical APDs are relatively potent D4 antagonists at clinical dosages, including clozapine, and risperidone. The D4 antagonist, L745870, blocked the ability of clozapine, but not lurasidone, to reverse the NOR deficit in rats. The purpose of this study was to determine the effects of a selective D4 agonist and antagonist, alone, and as pretreatment with lurasidone, on neurotransmitter efflux in mouse medial prefrontal cortex (mPFC) and dorsal striatum (dSTR), using in vivo microdialysis. PD168077 alone, and in combination with sub-effective dose lurasidone, increased DA and acetylcholin...Continue Reading

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Mentioned in this Paper

Striatonigral Degeneration, Infantile (Disorder)
Study
In Vivo
Atypical Antipsychotic [EPC]
Adrenal Cortex Diseases
Dopamine D4 receptor
Neostriatum
L 745870
Extracellular
Schizophrenia

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