Effects of Endothelin-Induced Prefrontal Cortical Lesions on Delay Discounting in the Rat

Stroke is one of the most prominent causes of neurological disability, and the number of stroke cases worldwide is expected to grow due to increases in both average life span and population. As such, new methods for both acute treatment and poststroke rehabilitation will be increasingly necessary. Although a number of approaches to restoring motor function poststroke are in development, there are few methods to alleviate the cognitive deficits caused by this disease. As well, there are very few preclinical models of stroke with a specific focus on higher-order cognitive functions. The goal of the current experiments was to examine the effects of bilateral ischemic lesions, produced by targeted microinjections of endothelin-1 (ET-1) in the medial (mPFC) and orbital (oPFC) prefrontal cortices of adult male Sprague-Dawley rats (n = 39) on inhibitory control as measured through a delay discounting paradigm. The ET-1 injections to the mPFC and oPFC resulted in average lesion volumes of 17.98 mm(3) +/- 2.841 mm(3) (Mean +/- SE) and 26.05 mm(3) +/- 4.052 mm(3) (Mean +/- SE), respectively. During delay discounting testing, wherein animals were offered a small, immediately available food reward versus a large, but delayed reward, it was found that animals with lesions to the oPFC were more likely to choose the immediately available reward as compared to their mPFC or control counterparts. We conclude that using ET-1 in the oPFC may be a new and viable method to study the effects of ischemic lesions on higher-order cognitive dysfunction poststroke.