Intramural Research Program, National Institutes of Health/National Institute on Drug Abuse, Baltimore, Maryland 21224, USA.
J Neurosci. 2013 Jan 2;33(1):214-26. doi: 10.1523/JNEUROSCI.2016-12.2013.
Relapse to maladaptive eating habits during dieting is often provoked by stress. Recently, we identified a role of dorsal medial prefrontal cortex (mPFC) neurons in stress-induced reinstatement of palatable food seeking in male rats. It is unknown whether endogenous neural activity in dorsal mPFC drives stress-induced reinstatement in female rats. Here, we used an optogenetic approach, in which female rats received bilateral dorsal mPFC microinjections of viral constructs coding light-sensitive eNpHR3.0-eYFP or control eYFP protein and intracranial fiber optic implants. Rats were food restricted and trained to lever press for palatable food pellets. Subsequently, pellets were removed, and lever pressing was extinguished; then the effect of bilateral dorsal mPFC light delivery on reinstatement of food seeking was assessed after injections of the pharmacological stressor yohimbine (an α-2 andrenoceptor antagonist) or pellet priming, a manipulation known to provoke food seeking in hungry rats. Dorsal mPFC light delivery attenuated yohimbine-induced reinstatement of food seeking in eNpHR3.0-injected but not eYFP-injected rats. This optical manipulation had no effect on pellet-priming-induced reinstatement or ongoing food-reinforced responding. Dorsal mPFC light delivery attenuated yohimbine-induced Fos immunoreactivity and disrupted neural activity during in vivo electrophysiological recording in awake rats. Optical stimulation caused significant outward currents and blocked electrically evoked action potentials in eNpHR3.0-injected but not eYFP-injected mPFC hemispheres. Light delivery alone caused no significant inflammatory response in mPFC. These findings indicate that intracranial light delivery in eNpHR3.0 rats disrupts endogenous dorsal mPFC neural activity that plays a role in stress-induced relapse to food seeking in female rats.
节食期间不良饮食习惯的复发通常是由压力引起的。最近，我们发现背内侧前额叶皮层（mPFC）神经元在雄性大鼠的应激诱导的美味食物寻求复燃中起作用。尚不清楚内源性背侧 mPFC 神经元活动是否会驱动雌性大鼠的应激诱导复燃。在这里，我们使用光遗传学方法，其中雌性大鼠接受双侧背侧 mPFC 病毒构建体的微注射，编码光敏感的 eNpHR3.0-eYFP 或对照 eYFP 蛋白，并进行颅内光纤植入。大鼠接受食物限制并接受训练以按压杠杆以获得美味食物丸。随后，取出药丸，按压杠杆被熄灭；然后评估双侧背侧 mPFC 光传递对注射药物应激剂育亨宾（α-2 肾上腺素受体拮抗剂）或丸剂引发后食物寻求的恢复的影响，这是一种已知会引起饥饿大鼠食物寻求的操作。背侧 mPFC 光传递减弱了 eNpHR3.0 注射而不是 eYFP 注射大鼠中育亨宾诱导的食物寻求恢复。这种光学操作对丸剂引发的恢复或正在进行的食物强化反应没有影响。背侧 mPFC 光传递减弱了育亨宾诱导的 Fos 免疫反应，并在清醒大鼠的体内电生理记录中破坏了神经活动。光刺激引起显著的外向电流，并阻断了 eNpHR3.0 注射而不是 eYFP 注射 mPFC 半球中的电诱发动作电位。光传递本身不会引起 mPFC 中的明显炎症反应。这些发现表明，在 eNpHR3.0 大鼠中进行颅内光传递会破坏内源性背侧 mPFC 神经活动，该活动在雌性大鼠的应激诱导的食物寻求复燃中起作用。
