Impaired monoamine neural system in the mPFC of SHRSP/Ezo as an animal model of attention-deficit/hyperactivity disorder

被引：3

作者：

Suzuki, Naoya ^{[1
]}

Hiraide, Sachiko ^{[1
]}

Shikanai, Hiroki ^{[1
,2
]}

Isshiki, Takeru ^{[1
]}

Yamaguchi, Taku ^{[3
]}

Izumi, Takeshi ^{[1
,2
]}

Iizuka, Kenji ^{[1
]}

机构：

[1] Hlth Sci Univ Hokkaido, Fac Pharmaceut Sci, Dept Pharmacol, 1757 Kanazawa, Ishikari, Hokkaido 0610293, Japan

[2] Hlth Sci Univ Hokkaido, Adv Res Promot Ctr, 1757 Kanazawa, Ishikari, Hokkaido 0610293, Japan

[3] Nagasaki Int Univ, Fac Pharmaceut Sci, Dept Pharmacotherapeut & Neuropsychopharmacol, 2825-7 Huis Ten Bosch Sasebo, Nagasaki, Nagasaki 8593298, Japan

来源：

JOURNAL OF PHARMACOLOGICAL SCIENCES | 2024年 / 154卷 / 02期

关键词：

Attention-deficit/hyperactivity disorder (ADHD); Dopamine transporter (DAT); Medial prefrontal cortex (mPFC); Monoamine reuptake inhibitor; Stroke-prone spontaneously hypertensive rat (SHRSP)/Ezo; DEFICIT HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER; BEHAVIOR; RAT; PATHOPHYSIOLOGY; CORTEX; ADHD;

D O I：

10.1016/j.jphs.2023.12.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood-onset psychiatric disorder. We investigated the effects of systemic administration of monoamine reuptake inhibitors on long-term potentiation (LTP) formation and monoamine release in the medial prefrontal cortex (mPFC) of the stroke-prone spontaneously hypertensive rat (SHRSP)/Ezo, an animal model of ADHD, and its genetic control, Wistar Kyoto (WKY)/Ezo, to elucidate the functional changes in the mPFC monoamine neural system. Methylphenidate (dopamine (DA) and noradrenaline (NA) reuptake inhibitor) and desipramine (NA reuptake inhibitor) improved LTP formation defects in the mPFC of SHRSP/Ezo, suggesting that NA or both DA and NA are required for improvement of impaired LTP. Methylphenidate increased mPFC DA in both WKY/Ezo and SHRSP/Ezo, but the increase was greater in the former. GBR-12909 (DA reuptake inhibitor) increased mPFC DA in WKY/Ezo but had no effect in SHRSP/Ezo. This may be because DA transporter in SHRSP/Ezo is functionally impaired and contributes less to DA reuptake, so its inhibition did not increase DA level. Meanwhile, basal DA levels in the mPFC of SHRSP/Ezo were paradoxically decreased. These results suggest that functional changes in the DA and NA neural system in the frontal lobe are involved in the pathology of ADHD.

引用

页码：61 / 71

页数：11

共 32 条

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