Addiction

1 Key elements of addiction

• Addictive substances are highly reinforcing.
• They are reinforcing because they induce pleasure.
• Pleasure leads to ‘liking’ the effects of addictive substances.
• ‘Liking’ a substance can become conditioned to substance-related cues.
• ‘Wanting’ a substance can occur at the expense of ‘liking’ the substance.
• Excessive ‘wanting’ can lead to a loss of control of substance use.
• Substance use habits are unconscious—they are automatic.
• Craving for substances may occur following prolonged abstinence.
• Craving may trigger substance relapse

• 成瘾物质具有高度强化作用。
• 它们正在强化，因为它们会引起快乐。
• 快乐导致“喜欢”成瘾物质的效果。
• “喜欢”一种物质可能会受到与物质相关的线索的影响。
• “想要”某种物质的发生可能会以牺牲“喜欢”该物质为代价。
• 过度的“想要”会导致对物质使用的失控。
• 物质使用习惯是无意识的——它们是自动的。
• 戒断滥用物质会导致重复使用。
• 长期戒酒后可能会出现对物质的渴望。
• 渴望可能会引发物质复发

2 Neurobiological processes in addiction

成瘾中的神经生物学过程

• The brain controls necessary motivational and cognitiv processes.
• These processes involve a network of independent and overlapping brain circuits.
• These processes involve reward, motivation, learning/memory, and cognition.
• Reward involves dopamine in the ventral striatum.
• Learning involves dopamine in the ventral tegmental area and ventral striatum.
• Memory involves glutamate in the amygdala and hippocampus.
• Motivation and drive involve GABA and dopamine in the orbitofrontal cortex.
• Cognition involves dopamine and glutamate in the prefrontal cortex.
• These processes are disrupted by substances of addiction

• 大脑控制必要的动机和认知过程。
• 这些过程涉及一个由独立和重叠的大脑回路组成的网络。
• 这些过程涉及奖励、动机、学习/记忆和认知。
• 奖励涉及腹侧纹状体中的多巴胺。
• 学习涉及腹侧被盖区和腹侧纹状体的多巴胺。
• 记忆涉及杏仁核和海马体中的谷氨酸。
• 动机和驱动力涉及眶额叶皮层中的 GABA 和多巴胺。
• 认知涉及前额叶皮层中的多巴胺和谷氨酸。
• 这些过程被成瘾物质打乱

3 Pharmacodynamics of addictive substances

成瘾物质的药效学

• Pharmacodynamics refers to the effect of substances on the body.
• The pharmacodynamic effects of substances take place at receptors.
• Agonists mimic the effects of neurotransmitters at receptors.
• Antagonists block the effects of neurotransmitters at receptors.
• Addictive substances can alter brain pharmacodynamics.
• Brain pharmacodynamics can be influenced by genetics.

• 药效学是指物质对身体的影响。
• 物质的药效学作用发生在受体处。
• 激动剂模拟神经递质对受体的作用。
• 拮抗剂阻断神经递质对受体的作用。
• 成瘾物质可以改变大脑药效学。
• 大脑药效学会受到遗传学的影响。

4 The dopamine system and addiction

多巴胺系统和成瘾

• Dopamine release is involved in the reinforcing effects of addictive substances.
• Dopamine release can be blunted by substance abuse.
• Dopamine release is involved in drug craving.
• Dopamine receptors are reduced during substance addiction withdrawal.
• Medications that boost dopamine functioning may be useful in substance addiction.
• Reductions in dopamine functioning may predispose people to substance addiction

• 多巴胺的释放与成瘾物质的强化作用有关。
• 药物滥用会减慢多巴胺的释放。
• 多巴胺释放与药物渴望有关。
• 物质成瘾戒断期间多巴胺受体减少。
• 促进多巴胺功能的药物可能对物质成瘾有用。
• 多巴胺功能降低可能使人易患物质成瘾

5 The GABA system and addiction

GABA 系统和成瘾

• GABA is the major inhibitory neurotransmitter in the brain.
• GABA binds with GABA-a and GABA-b receptors to inhibit neuronal activity.
• Substances of abuse can downregulate or upregulate the GABA system.
• GABA-b receptors modulate substance reward and reinforcement behaviours.
• Disturbances to the GABA system may pre-date substance addiction.
• Compounds that target the GABA system may help in the treatment of addiction

• GABA 是大脑中主要的抑制性神经递质。
• GABA 与 GABA-a 和 GABA-b 受体结合以抑制神经元活动。
• 滥用物质可以下调或上调 GABA 系统。
• GABA-b 受体调节物质奖励和强化行为。
• 对 GABA 系统的干扰可能早于物质成瘾。
• 靶向 GABA 系统的化合物可能有助于治疗成瘾

6 The glutamate system and addiction

谷氨酸系统和成瘾

• Addiction involves enduring neuroplasticity in the reward circuitry of the brain.
• Neuroplasticity is a result of glutamate-dependent long-term potentiation.
• Glutamate is an excitatory neurotransmitter.
• Glutamate release is involved in alcohol and drug relapse in response to drug cues.
• There are changes in glutamate receptor functioning in substance addiction.
• Medications that reduce glutamate tone may prevent alcohol and drug relapse

• 成瘾涉及大脑奖励回路中持久的神经可塑性。
• 神经可塑性是谷氨酸依赖长期增强的结果。
• 谷氨酸是一种兴奋性神经递质。
• 谷氨酸的释放与酒精和药物复发有关。
• 物质成瘾中谷氨酸受体功能发生变化。
• 降低谷氨酸调理的药物可以防止酒精和药物复发

7 The opioid system and addiction

阿片类药物系统和成瘾

• 大脑包含一个复杂的内源性阿片肽系统。
• 这些肽称为内啡肽、脑肽和强啡肽。
• 内啡肽优先与 mu 阿片受体 （mOR） 结合。
• 脑蛋白优先与 δ 受体 （dOR） 结合。
• 强啡肽优先与 κ 受体 （kOR） 结合。
• 阿片类药物，如海洛因和吗啡，也会刺激 mOR。
• mOR 在物质成瘾中上调
• mOR 的遗传多态性会影响对酒精的主观反应。

• The brain contains a complex system of endogenous opioid peptides.
• These peptides are called endorphins, encephalins, and dynorphin.
• Endorphins preferentially bind to the mu opioid receptor (mOR).
• Encephalins preferentially bind to the delta receptor (dOR).
• Dynorphin preferentially binds to the kappa receptor (kOR).
• Opiates, such as heroin and morphine, also stimulate the mOR.
• The mOR is upregulated in substance addiction
• Genetic polymorphisms at the mOR influence subjective responses to alcohol.

8 Nicotine addiction

• Nicotine is a stimulant that is the main psychoactive element of cigarettes.
• Nicotine is an agonist at nicotinic acetylcholine receptors in the brain.
• Nicotine in smoked tobacco is addictive.
• Nicotine causes disturbances to reward and cognitive processing.
• Cigarette smoking presents considerable health risks.
• Cigarette smoking induces high costs on healthcare resources.
• Smoking cessation medications and safer nicotine products (e.g. e-cigs) are now available to treat nicotine addiction

• 尼古丁是一种兴奋剂，是香烟的主要精神活性成分。
• 尼古丁是大脑中烟碱乙酰胆碱受体的激动剂。
• 烟熏烟草中的尼古丁会让人上瘾。
• 尼古丁会干扰奖励和认知处理。
• 吸烟会带来相当大的健康风险。
• 吸烟会导致医疗保健资源的高成本。
• 戒烟药物和更安全的尼古丁产品（例如电子烟）现在可用于治疗尼古丁成瘾

9 Appetite hormones and addiction

食欲、荷尔蒙和成瘾

• Appetite and feeding are regulated by hormones that affect the brain.
• These hormones signal the present energy state of the body.
• These hormones can regulate reward and motivational processes.
• Ghrelin is an orexigenic gut hormone that activates reward circuitry.
• Ghrelin increase the consumption of food, but also drugs of addiction.
• Glucagon-like peptide-1 (GLP-1) is an anorexigenic hormone.
• GLP-1 reduces the consumption of food and drugs of addiction.

• 食欲和进食受影响大脑的激素调节。
• 这些激素是身体当前能量状态的信号。
• 这些激素可以调节奖励和激励过程。
• 生长素释放肽是一种产食欲的肠道激素，可激活奖励回路。
• 生长素释放肽增加了食物的消费，但也增加了成瘾药物的消费。
• 胰高血糖素样肽-1 （GLP-1） 是一种厌食激素。
• GLP-1 减少食物和成瘾药物的消费。

10 Conclusion and overview

• Substances of addiction are highly reinforcing because they induce pleasure.
• Cocaine and amphetamines trigger exaggerated increases in dopamine.
• GABA is the major inhibitory neurotransmitter in the brain.
• Compounds that target the GABA system may help in the treatment of addiction.
• Addiction involves glutamate-dependent neuroplasticity in the brain.
• Medications that target glutamate may be efficacious in preventing drug relapse

• The brain contains a complex system of endogenous opioid peptides.
• The mu opioid receptor appears to be involved in substance abuse and addiction.
• Compounds that target the mu opioid receptor system may help treat addiction.
• Nicotine causes disturbances in reward and cognitive processing.
• Smoking cessation medications are available to treat nicotine addiction.
• Appetite and feeding are regulated by hormones that affect the brain.
• These hormones can regulate reward and motivational processes.

 • 成瘾物质具有高度强化作用，因为它们会引起快乐。
 • 可卡因和安非他明会引发多巴胺的过度增加。
 • GABA 是大脑中主要的抑制性神经递质。
 • 靶向 GABA 系统的化合物可能有助于治疗成瘾。
 • 成瘾涉及大脑中谷氨酸依赖性的神经可塑性。
 • 靶向谷氨酸的药物可能有效预防药物复发

 • 大脑包含一个复杂的内源性阿片肽系统。
 • mu 阿片受体似乎与药物滥用和成瘾有关。
 • 靶向 μ 阿片受体系统的化合物可能有助于治疗成瘾。
 • 尼古丁会干扰奖励和认知处理。
 • 戒烟药物可用于治疗尼古丁成瘾。
 • 食欲和进食受影响大脑的激素调节。
 • 这些激素可以调节奖励和激励过程。