The antipsychotic-like effects in rodents of YQA31 involve dopamine D3 and 5-HT1A receptor.

Abstract

BACKGROUND:

We previously reported that YQA31 is a dopamine D3 receptor antagonist with modest 5-HT1A receptor affinity and that it exhibits antipsychotic properties in animal models of schizophrenia. However, the contributions of D3 and 5-HT1A receptors in the anti-psychotic effects of YQA31 are not clear. The current study evaluated the role of these two receptors in the effect of YQA31 on the hyperactivity and novel object recognition deficit in mice.

METHODS:

We used dopamine D3 receptor knockout mice and 5-HT1A receptor antagonist WAY100635 pretreatment, respectively, to investigate the involvement of these receptors in the effects of YQA31. The anti-psychotic effects were tested by inducing hyperlocomotion with methamphetamine or MK-801 and by inducing novel object recognition deficit with MK-801, which are the animal models to represent a positive symptom and a cognitive disorder.

RESULTS:

YQA31 significantly inhibited MK-801-induced hyperlocomotion and novel object recognition deficit in WT mice, which was significantly inhibited by dopamine D3 receptor knockout. The 5-HT1A receptor antagonist, WAY100635, also blocked the effect of YQA31 in MK-801-induced novel object recognition deficit but not hyperlocomotion. The effect of YQA31 on methamphetamine-induced hyperlocomotion was not reversed by either dopamine D3 receptor knockout or WAY100635 pretreatment.

CONCLUSIONS:

These results demonstrate the different roles of dopamine D3 and 5-HT1A receptors in the anti-psychotic effects of YQA31. Both dopamine D3 and 5-HT1A receptors contributed to the effects of YQA31 on the inhibition of MK-801-induced novel object recognition deficit, and the dopamine D3 receptor mediated the inhibiting effect of YQA31 on hyperlocomotion induced by MK-801.

• Authors: Hong-Yan Gou, Xue Sun, Fei Li, Zhi-Yuan Wang, Ning Wu, Rui-Bin Su, Bin Cong, Jin Li
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 69 Issue 6 Pg. 1125-1130 (Dec 2017) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 29128790 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

Chemical References

• Antipsychotic Agents
• Benzothiazoles
• Piperazines
• Pyridines
• Receptors, Dopamine D3
• Y-QA31
• Receptor, Serotonin, 5-HT1A
• Methamphetamine
• Dizocilpine Maleate
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide

Topics

• Animals
• Antipsychotic Agents (pharmacology)
• Benzothiazoles (pharmacology)
• Cognition Disorders (drug therapy, physiopathology)
• Disease Models, Animal
• Dizocilpine Maleate (pharmacology)
• Hyperkinesis (drug therapy)
• Male
• Methamphetamine (pharmacology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Piperazines (pharmacology)
• Pyridines (pharmacology)
• Receptor, Serotonin, 5-HT1A (drug effects, metabolism)
• Receptors, Dopamine D3 (drug effects, genetics, metabolism)
• Recognition, Psychology (drug effects)