Activation of metabotropic glutamate 2/3 receptors attenuates methamphetamine-induced hyperlocomotion and increase in prefrontal serotonergic neurotransmission

被引：15

作者：

Ago, Yukio ^{[3
]}

Araki, Ryota ^{[3
]}

Yano, Koji ^{[3
]}

Hiramatsu, Naoki ^{[3
]}

Kawasaki, Toshiyuki ^{[3
,4
]}

Chaki, Shigeyuki ^{[5
]}

Nakazato, Atsuro ^{[6
]}

Onoe, Hirotaka ^{[4
]}

Hashimoto, Hitoshi ^{[1
,2
,7
,8
]}

Baba, Akemichi ^{[7
]}

Takuma, Kazuhiro ^{[3
]}

Matsuda, Toshio ^{[1
,2
,3
,8
]}

机构：

[1] Kanazawa Univ, Osaka Univ, United Grad Sch Child Dev, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Hamamatsu Univ Sch Med, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Med Pharmacol, Suita, Osaka 5650871, Japan

[4] RIKEN, Funct Probe Res Lab, Ctr Mol Imaging Sci, Kobe MI R&D Ctr,Chuo Ku, Kobe, Hyogo 6500047, Japan

[5] Taisho Pharmaceut Co Ltd, Mol Funct & Pharmacol Labs, Kita Ku, Saitama 3319530, Japan

[6] Taisho Pharmaceut Co Ltd, Strateg Planning Drug Discovery, R&D Headquarters Pharmaceut Operat, Kita Ku, Saitama 3319530, Japan

[7] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Mol Neuropharmacol, Suita, Osaka 5650871, Japan

[8] Osaka Univ, Grad Sch Med, Osaka Hamamatsu Joint Res Ctr Child Mental Dev, Dept Expt Dis Model, Suita, Osaka 5650871, Japan

来源：

PSYCHOPHARMACOLOGY | 2011年 / 217卷 / 03期

关键词：

Metabotropic glutamate (mGlu) 2/3 receptors; Methamphetamine; Hyperlocomotion; Serotonin (5-HT); Dopamine (DA); Noradrenaline (NA); Prefrontal cortex; Nucleus accumbens; DOPAMINE RELEASE; D-AMPHETAMINE; AGONIST LY379268; PHARMACOLOGICAL CHARACTERIZATION; ALPHA-1B-ADRENERGIC RECEPTORS; BEHAVIORAL SENSITIZATION; CORTEX; MICE; PHENCYCLIDINE; RATS;

D O I：

10.1007/s00213-011-2295-3

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Metabotropic glutamate (mGlu) 2/3 receptor agonists inhibit amphetamine- and phencyclidine-induced hyperlocomotion. The mechanism for the antipsychotic effect of mGlu2/3 receptor agonists was studied in a hypoglutamatergic model, but not a hyperdopaminergic model. To study the mechanism for the antipsychotic effect of the agonist in the hyperdopaminergic model, this study examined the effects of the selective mGlu2/3 receptor agonist MGS0028 on methamphetamine-induced hyperlocomotion and the increases in extracellular levels of serotonin, dopamine, noradrenaline, and glutamate in the prefrontal cortex and nucleus accumbens of mice. Systemic administration of MGS0028 attenuated methamphetamine-induced hyperlocomotion in a dose-dependent manner. Microdialysis studies showed that MGS0028 significantly inhibited methamphetamine-induced increases in the extracellular serotonin, but not dopamine and noradrenaline, levels in the prefrontal cortex, and it did not affect methamphetamine-induced increases in the extracellular amine levels in the nucleus accumbens. Methamphetamine did not affect the glutamate release in the prefrontal cortex and nucleus accumbens. Local application of MGS0028 into the prefrontal cortex also attenuated methamphetamine-induced hyperlocomotion and increases in the extracellular serotonin levels in the prefrontal cortex. Moreover, MGS0028 did not affect methamphetamine-induced hyperlocomotion in the mice pretreated with p-chlorophenylalanine, a serotonin synthesis inhibitor. Activation of prefrontal mGlu2/3 receptors inhibits the psychomotor stimulant effect of methamphetamine in mice, and the prefrontal serotonergic system may be involved in this effect. The finding provides evidence that prefrontal mGlu2/3 receptors are functionally coupled with the serotonergic system.

引用

页码：443 / 452

页数：10

共 45 条

[1]

Ritanserin reverses repeated methamphetamine-induced behavioral and neurochemical sensitization in mice [J].