Lindenbach David, Seamans Jeremy K, Phillips Anthony G
Djavad Mowafaghian Centre for Brain Health, Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Behav Brain Res. 2019 Jan 1;356:266-270. doi: 10.1016/j.bbr.2018.09.002. Epub 2018 Sep 7.
Previous studies confirm that brief electrical stimulation of glutamatergic afferents from the ventral subiculum (vSub) can significantly enhance dopamine release in the ventral striatum for an extended duration (>20 min). However, the functional significance of this effect on motivated behavior remains to be specified. Here we tested the hypothesis that brief electrical stimulation of the ventral subiculum (20 Hz for 10 s) might increase effort expenditure for food rewards. Motivation was assessed by a progressive ratio lever pressing task, which requires continuous escalation of the numbers of lever presses to receive each subsequent sucrose pellet, eventually resulting in the failure to achieve the required ratio for a food reward. vSub stimulation at the start of a session did not affect the rate or total number of lever presses prior to reaching the "break point". In contrast, stimulation of the vSub with identical parameters on a post break point trial resulted in a significant increase in total responses. These findings demonstrate that activation of the vSub with parameters that modulate dopamine efflux in the nucleus accumbens can re-activate goal-directed behavior after failure to achieve a goal. Our data highlight a possible role for the vSub in the pathophysiology and potential treatment of motivational processes linked to psychiatric disease.
先前的研究证实,对来自腹侧下托(vSub)的谷氨酸能传入神经进行短暂电刺激,可在较长时间(>20分钟)内显著增强腹侧纹状体中的多巴胺释放。然而,这种效应在动机行为方面的功能意义仍有待明确。在此,我们测试了这样一种假设,即对腹侧下托进行短暂电刺激(20赫兹,持续10秒)可能会增加获取食物奖励时的努力付出。通过渐进比率杠杆按压任务评估动机,该任务要求不断增加杠杆按压次数以获得后续的每颗蔗糖颗粒,最终导致无法达到获得食物奖励所需的比率。在实验开始时对vSub进行刺激,在达到“断点”之前,不会影响杠杆按压的速率或总数。相比之下,在断点后试验中用相同参数刺激vSub会导致总反应显著增加。这些发现表明,用调节伏隔核中多巴胺流出的参数激活vSub,可以在目标未达成后重新激活目标导向行为。我们的数据突出了vSub在与精神疾病相关的动机过程的病理生理学和潜在治疗中的可能作用。