Biopsychological research on the role of brain acetylcholine in intracranial self-stimulation behavior

脑乙酰胆碱在颅内自刺激行为中作用的生物心理学研究

• 批准号: 11610074
• 负责人: NAKAMURA Masato
• 金额: $ 1.66万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11610074/
• 关键词: Mesopontine tegmentum; Cholinergic pathway; Fos; Choline acetyltransferase; Intracranial self-stimulation (ICSS); Microdialvsis; Nicotinic receptor; Reward; アセチルコリン; 腹側被蓋野; 二重染色; GABA; 脳内自己刺激

We investigated the role of cholinergic pathway that projects from mesopontine tegmentum, i.e., pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDTg), to ventral tegmental area (VTA), in the rat brain reward system.Using double immunostaining for Fos as a marker of neuronal activity and choline acetyltransferase as a marker of cholinergic neurons, we investigated whether or not intracranial self stimulation (ICSS) of the medial forebrain bundle (MFB) induces Fos expression within PPTg and LDTg. ICSS of the MFB for one hour induced a large increase in the number of cells that expressed Fos in both the LDTg and PPTg, when compared to control brains. However, most of choline acetyltransferase positive cells in these regions did not express Fos. We also examined, using microdialysis, whether ICSS of the MFB increases acetylcholine efflux in the VTA, a terminal region of the mesopontine tegmentum cholinergic pathway. One-hour ICSS significantly increased acetylcholine efflux in the VTA. The results indicate that ICSS of the MFB may increase terminal acetylcholine release without affecting expression of Fos within cell bodies in the cholinergic pathway of the mesopontine tegmentum.Next, we used the rate-frequency curve-shift procedure to evaluate the effect of nicotinic blockers on the threshold of ICSS reward. The rats were implanted with an electrode in the MFB and an ipsilateral guide cannula in the VTA. Nicotine blockers were continuously infused through reverse dialysis into the VTA two hours before and during the self-stimulation. Mecamylamine (25-100 mM), the channel blocker of nicotinic acetylcholine receptors, sifted rate-frequency curves to the right by a mean of 14.6-35.5% in a dose-related manner. Mecamylamine decreased maximum bar-pressing rates when the shifts were large. Thus, nicotinic receptors in the VTA seem to be important for the mediation of the rewarding effect of the ICSS in rats.

我们研究了从中桥脑被盖投射的胆碱能通路的作用，即，本研究采用Fos和胆碱乙酰转移酶双标免疫组化方法，观察了内侧前脑束（MFB）颅内自我刺激（ICSS）是否诱导大鼠大脑皮层前额叶脚桥被盖核（PPTg）和背外侧被盖核（LDTg）内Fos的表达。与对照组相比，MFB的ICSS一小时诱导了LDTg和PPTg中表达Fos的细胞数量的大量增加。而这些区域的胆碱乙酰转移酶阳性细胞大多不表达Fos。我们还研究，使用微透析，是否ICSS的MFB增加乙酰胆碱流出的腹侧被盖区，一个终端区域的中桥脑被盖胆碱能通路。1小时ICSS显著增加VTA中的乙酰胆碱流出。结果表明，ICSS的MFB可能会增加终末乙酰胆碱的释放，而不影响表达Fos的细胞体中的胆碱能通路的中桥脑tegmentum.Next，我们使用率频率曲线移动程序来评估烟碱受体阻滞剂的ICSS奖励阈值的影响。在大鼠的MFB中植入电极，在VTA中植入同侧引导套管。在自我刺激前两小时和自我刺激期间，通过反向透析将尼古丁阻滞剂持续输注到VTA中。烟碱性乙酰胆碱受体通道阻滞剂美加明（25-100 mM）以剂量相关方式使速率-频率曲线向右偏移平均14.6-35.5%。当位移较大时，美加明降低了最大压杆速率。因此，在VTA的烟碱受体似乎是重要的ICSS在大鼠的奖励效果的调解。

项目成果

Nakahara, D.: "Lack of glucocorticoids attenuates the self-stimulation-induced increase in the in vivo synthesis rate of dopamine but serotonin in the rat nucleus accumbens"European Journal of Neuroscience. 12. 1495-1500 (2000)

Nakahara, D.：“缺乏糖皮质激素会减弱自我刺激引起的大鼠伏隔核中多巴胺和血清素体内合成率的增加”《欧洲神经科学杂志》。

Nakahara, D.: "Differential effect of immobilization stress on in vivo synthesis rate of monoamines in medial prefrontal cortex and nucleus accumbens of conscious rats"Synapse. 32. 238-242 (1999)

Nakahara, D.：“固定应激对清醒大鼠内侧前额皮质和伏隔核体内单胺合成率的不同影响”突触。

D. Nakahara: "Differential effect of immobilization stress on in vivo synthesis rate of monoamines in medial prefrontal cortex and nucleus accumbens of conscious rats"Synapse. 32. 238-242 (1999)

D. Nakahara：“固定应激对清醒大鼠内侧前额皮质和伏核体内单胺合成率的不同影响”突触。

Y. Ishida: "lmmunohistochemical characterisation of Fospositive cells in brainstem monoaminergic nuclei following intracranialself-stimulation of the medial forebrain bundle in the rat"European Journal of Neuroscience. 12(8). 1600-8 (2001)

Y. Ishida：“大鼠内侧前脑束颅内自刺激后脑干单胺能核中 Fos 阳性细胞的免疫组织化学特征”《欧洲神经科学杂志》。

D. Nakahara: "Lack of glucocorticoids attenuates the selfstimulation-induced increase in the in vivo synthesis rate of dopamine but not serotonin in the rat nucleus accumbens"European Journal of Neuroscience. 12. 149-1500 (2000)

D. Nakahara：“缺乏糖皮质激素会减弱自我刺激引起的大鼠伏隔核中多巴胺体内合成率的增加，但不会减弱血清素的增加”《欧洲神经科学杂志》。