Yeomans J S, Takeuchi J, Baptista M, Flynn D D, Lepik K, Nobrega J, Fulton J, Ralph M R
Department of Psychology, University of Toronto, Toronto, Ontario, Canada M5S 3G3.
J Neurosci. 2000 Dec 1;20(23):8861-7. doi: 10.1523/JNEUROSCI.20-23-08861.2000.
Oligonucleotides targeting M5 muscarinic receptor mRNA were infused for 6 d into the ventral tegmental area of freely behaving rats trained to bar-press for lateral hypothalamic stimulation. The bar-pressing rate was determined at a range of frequencies each day to evaluate the effects of infusions on reward. M5 antisense oligonucleotide (oligo) infusions increased the frequency required for bar pressing by 48% over baseline levels, with the largest increases occurring after 4-6 d of infusion. Two control oligos had only slight effects (means of 5 and 11% for missense and sense oligos, respectively). After the infusion, the required frequency shifted back to baseline levels gradually over 1-5 d. Antisense oligo infusions decreased M5 receptors on the ipsilateral, but not the contralateral, side of the ventral tegmentum, as compared with a missense oligo. Therefore, M5 muscarinic receptors associated with mesolimbic dopamine neurons seem to be important in brain-stimulation reward.
将靶向M5毒蕈碱受体mRNA的寡核苷酸注入自由活动的大鼠腹侧被盖区，这些大鼠经过训练通过按压杠杆以获得下丘脑外侧刺激。每天在一系列频率下测定按压杠杆的速率，以评估注入对奖赏的影响。注入M5反义寡核苷酸（oligo）使按压杠杆所需频率比基线水平增加了48%，最大增幅出现在注入4 - 6天后。两种对照寡核苷酸只有轻微影响（错义寡核苷酸和正义寡核苷酸的均值分别为5%和11%）。注入后，所需频率在1 - 5天内逐渐恢复到基线水平。与错义寡核苷酸相比，反义寡核苷酸注入使腹侧被盖区同侧而非对侧的M5受体减少。因此，与中脑边缘多巴胺神经元相关的M5毒蕈碱受体似乎在脑刺激奖赏中很重要。
