Hogarth Samuel J, Djouma Elvan, van den Buuse Maarten
School of Psychology and Public Health, Department of Psychology and Counselling, La Trobe University, Melbourne 3086, VIC, Australia.
School of Life Sciences, Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne 3086, VIC, Australia.
Brain Sci. 2020 May 1;10(5):270. doi: 10.3390/brainsci10050270.
Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.
酒精使用障碍（AUD）是一种因长期接触乙醇而引发的有害疾病。脑源性神经营养因子（BDNF）表达降低与AUD及酒精成瘾有关，然而，大脑中BDNF信号激活对自愿性酒精摄入量恢复和复发的影响尚不清楚。因此，我们在操作性条件反射箱中训练雄性和雌性斯普拉格-道利大鼠自行摄入10%的乙醇溶液。在基线获取和渐进比率（PR）分析之后，大鼠在酒精杠杆消退期间被分为药物组和溶剂对照组。动物们连续两周每天接受腹腔注射BDNF受体TrkB激动剂7,8-二羟基黄酮（7,8-DHF）或溶剂对照。在酒精自我给药获取期间，雄性大鼠与酒精相关的杠杆按压绝对次数显著更高，且PR断点更高。然而，在调整体重后，两性之间的乙醇摄入量并无差异，且雌性大鼠的PR断点高于雄性大鼠。消退后，在调整体重后，7,8-DHF预处理并未改变雄性大鼠酒精引发的恢复行为。相比之下，在雌性大鼠中，恢复期间7,8-DHF处理显著提高了经体重调整后的潜在乙醇摄入量，但未改变主动杠杆按压的绝对次数。在自动光电管笼中对自发运动活动的分析表明，7,8-DHF的作用与多动无关。这些结果表明，TrkB受体的刺激可能导致AUD中的奖赏渴望和复发，尤其是在雌性大鼠中。
