TOP ＞ シンポジウム（Symposium）

Symposium The Addicted brain-From substance abuse to gambling and gaming disorders シンポジウム 依存する脳ー薬物依存からギャンブル、ゲーム依存までー 7月26日（金）8:35～9:03　第2会場（朱鷺メッセ　2F　メインホールA） 2S02m-1 ストレスによるコカイン欲求の増強機構 Katsuyuki Kaneda（金田 勝幸） 金沢大学・薬・薬理 Stress augments cocaine craving in addicted individuals. To elucidate neural mechanisms underlying this effect of stress, we have developed an experimental paradigm combining cocaine-induced conditioned place preference (CPP) test with restraint stress. After cocaine conditioning, acute (30 min) restraint stress exposure immediately before posttest significantly increased cocaine CPP scores. It has been reported that, during stress exposure, the level of extracellular noradrenaline (NA) is increased in the laterodorsal tegmental nucleus (LDT), which sends cholinergic projections to dopamine neurons in the ventral tegmental area, and in the medial prefrontal cortex (mPFC). Thus, we investigated the roles of NA in these brain regions for stress-induced augmentation of cocaine CPP. Intra-LDT injection of an α2 adrenoceptor antagonist attenuated the stress-induced enhancement of cocaine CPP. In vitro whole-cell recordings revealed that α2 adrenoceptor stimulation reduced GABAergic inputs to LDT cholinergic neurons in slices obtained from cocaine- but not saline-treated rats. These findings suggest that the relative excitation of LDT cholinergic neurons by α2 adrenoceptor-mediated disinhibition after repeated cocaine exposure contributes to the enhanced cocaine CPP. On the other hand, intra-mPFC injection of an α1 adrenoceptor antagonist reduced the stress-induced enhancement of cocaine CPP. Whole-cell recordings in mPFC slices demonstrated that α1 adrenoceptor stimulation directly excited mPFC pyramidal neurons and increased excitatory synaptic transmission. Additionally, silencing the neuronal activity of mPFC pyramidal cells with DREADD attenuated the stress-induced enhancement of cocaine CPP. These results indicate that excitation of mPFC pyramidal cells via α1 adrenoceptor stimulation contributes to stress-induced enhancement of cocaine CPP. Taken together, our findings suggest that stress-induced increases in NA transmission excite neuronal activity of the LDT and mPFC, resulting in the enhancement of cocaine craving. 7月26日（金）9:03～9:31　第2会場（朱鷺メッセ　2F　メインホールA） 2S02m-2 Identifying novel therapeutic targets for relapse prevention Andrew Lawrence（Lawrence Andrew） Florey Institute of Neuroscience & Mental Health Alcohol use disorders remain a major health risk within society, both relapse and heavy drinking being poorly controlled with current medications. We have recently undertaken a multidisciplinary study to examine the involvement of the cholinergic system in alcohol use and abuse. Following an extended history of alcohol use, we observed dysregulation of muscarinic receptor expression in the rat striatum. We also found that a centrally active and selective negative allosteric modulator (NAM) for the rat M5 muscarinic receptor (mAChR), ML375, selectively decreases ethanol self-administration and attenuates cue-induced reinstatement of ethanol-seeking in iP rats. We further show that in iP rats with an extensive history of ethanol intake that intra-dorsolateral (DL), but not intra-dorsomedial (DM), striatal injections of ML375 reduced ethanol self-administration to a similar extent as the nicotinic acetylcholine receptor (nAChR) ligand varenicline, which can reduce the reinforcing effects of ethanol in humans with AUD. These data implicate the DL striatum as a locus for the effects of cholinergic-acting drugs on ethanol-seeking in rats with a history of long-term ethanol use. Accordingly, we demonstrate in rats that selectively targeting the M5 mAChR can modulate both voluntary ethanol intake and cue-induced ethanol-seeking implicating the M5 mAChR as a potential novel target for pharmacotherapies aimed at treating alcohol use disorders. 7月26日（金）9:31～9:59　第2会場（朱鷺メッセ　2F　メインホールA） 2S02m-3 Goal-directed versus Stimulus-driven control in Gaming Disorders Young-Chul Jung（Jung Young-Chul）1,2 1Yonsei University College of Medicine, Department of Psychiatry 2Yonsei University College of Medicine, Institute of Behavioral Science in Medicine Gaming disorder (GD) is characterized by impaired control over gaming, and continuation of gaming despite the occurrence of negative consequences. We hypothesized that individuals with GD would demonstrate stronger stimulus-driven attention and weaker than goal-directed top-down attention, even while playing games that require real-time strategies. We measure and analyzed the cortical electrical activity by electroencephalography (EEG) and the autonomic nervous system activity with heart rate variability (HRV) in 33 individuals with GD and 29 HCs (mean age= 22.0 ± 2.8 years), while playing their favorite multiplayer online battle game. Each participant played three consecutive games, which usually took 30~40 minutes per game. The GD group showed weaker frontal theta and alpha activity (EEG) and weaker high-frequency bands (HRV), which indicated weaker cognitive control while playing games compared to the HC group. In addition, the weaker high frequency HRV correlated with weaker dorsal dorsolateral prefrontal cortex-inferior frontal gyrus connectivity (P=0.018) and stronger dorsal caudal putamen-postcentral gyrus connectivity (P=0.036). Our findings suggest an imbalance between the stimulus-driven attention network and the goal-directed top-down attention network in individuals with GD. These alterations should contribute to the impaired control over gaming, resulting in stimulus-driven compulsive gaming behaviors. 7月26日（金）9:59～10:27　第2会場（朱鷺メッセ　2F　メインホールA） 2S02m-4 ギャンブル障害の脳画像 Hidehiko Takahashi（高橋 英彦） 東京医歯大医歯総合認知行動・精神行動 Gambling disorder (Gambling addiction) has been categorized as a behavioral addiction in the international diagnostic criteria of mental disorders such as Diagnostic and Statistical Manual of Mental Disorders 5th edition. This shift was partly due to the fact that gamble addiction and substance addiction have much in common in clinical symptoms and brain science findings. In this symposium, we will show the common as well as differential findings between gamble addiction and substance addiction revealed by brain imaging research (magnetic resonance imaging and positron emission tomography). The results suggest that there might be various subtypes of gambling addiction. In the second half, we will present an example of identification of gambling addiction subtype suggested by our decision-making pattern and brain imaging research. We assessed the degree of loss aversion by economic games. High loss aversion group and low loss aversion group showed common and differential structural brain abnormalities measured by magnetic resonance imaging. Economics tool might be useful to assess cognitive intermediate phenotype (decision-making pattern). Our findings are in agreement with previous psychological notion, and might provide some hints for treatment strategy, especially or possible pharmacological treatment. Finally, we also want to discuss the possibility of an fMRI imaging biomarker of gambling disorder.