Nowadays, as substances are widely used across the nation, substance use disorder becomes a more prevalent disorder in the US. Drug addiction can be defined as compulsive drug use and a loss of control over drug-taking (Zangen, 2010). It is a severe psychological and pathological disorder, which risks body homeostasis and causes cognitive impairments. To understand how addiction develops, scientists did numerous experiments on lab animals, and eventually found out that dopamine and instrumental learning play predominant roles in motivating drug use and relapse.
Dopamine and drug addiction
Dopamine (DA) is a common neurotransmitter working in the mesolimbic pathway, from the ventral tegmental area (VTA) to the nucleus accumbens. The mesolimbic pathway producing a rewarding effect is a crucial pathway for the development of addiction. A study from Olds and Milner (1954, p.47) is the early evidence suggesting that dopamine plays a role in reward. Rat learns to press the level to obtain stimulation, which indicates that this stimulation activates dopaminergic rewarding systems. The development of addiction can be explained through the perspectives of instrumental conditioning. Base on the principle of instrumental conditioning, drug use, abuse and addiction are learned responses that are sensitive to their consequences and can therefore be understood as operant behaviors (Cahoon & Crosby, 1972). For instance, if the administration of drugs does not produce a reward effect (i.e. making people feel sick), the behavior of drug use is less likely to occur. Most of the drugs, such as amphetamine, are DA agonists that elevate the level of DA presence in the synaptic cleft. Base on the study from Wise (1996, p.19), administration of amphetamine on rats causing less lever pressing for electrical stimulation, indicates that increased DA activity producing long-lasting pleasure feeling. Self-administration of drug elevates extracellular dopamine levels more strongly than natural rewards such as food or sex (Wise, 2014). The rewarding effect of drugs is an unconditioned immediate positive reinforcement (Higgins & Petry, 1999). Thus, Drugs are conditioned stimulus evoked by reward effect which can elicit the instrumental response. To obtain or maintain an immediate reward effect, the learned instrumental response (behaviour of drug use) is reinforced, which more likely to occurs. Consequently, more frequent drug use results in repeated drug exposure which further promotes the development of addiction.
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Withdrawal and relapse
Chronic exposure of drug may result in development of tolerance leading to desensitization and down-regulation of receptor. Combined effects cause the receptor becoming insensitive. Consequently, higher dose of drug is required to achieve the same reward effect. Abstinence from the drug will result supra-optimal level of binding, causing decreased release of dopamine as well as the firing rate of dopaminergic neurons (Ghosh, 1997). PET scan of abstinent cocaine addicts shows decreased D2 receptor availability and extracellular DA in the striatum, which correlated with reductions of the excitability of the reward system (Chiara,2007). As a consequence, withdrawal from the drug produces opposite respond to acute administration, such as loss of motivation, depression and anxiety. As illustrated in the flood chart from Gawin (1986, p.43), addicts withdrawing from the drug will undergo three phases following a prolonged period of abstinence, which is crash, withdrawal and extinction. Eventually, addicts will either be abstinent from the drug or relapse. Ongoing drug use and relapse are driven by physiological and psychological craving which can be explained by the theory of instrumental conditioning. There are two widely accepted hypotheses explaining drug-seeking and drug-taking behaviour. Positive reinforcement mechanism highlights that the role of craving on maintaining the reward effect (i.e. high feeling) is invoked as a primary motivating force behind ongoing drug use and relapse (See, 2002). The hypothesis of positive reinforcement is supported by Wise (2014, p.39), who insists memory trace associated with the self-administration invokes ongoing drug use and relapse. The memory of an initial euphoric drug experience (reward effect) causes drug cravings which promotes drug-seeking behaviour (Bijerot, 1980; McAuliffe and Gordon, 1980). Compulsive drug-taking is reinforced to regain and maintain the reward effect. Contrarily, a negative reinforcement mechanism highlights that addicts learn to perform an instrumental response (drug use) in avoidance of expected withdrawal syndromes or terminate current aversive consequence. According to the study from Koob (2014, p.39), abstinent animals will increase in anxiety-like behavior, decreases in pain thresholds, and increases in reward thresholds during withdrawal from all major drugs of abuse. Koob (2014, p.39) emphasises that withdrawal syndromes are characterised by the combination of decreased dopaminergic rewarding activities and activation of anti-reward system. The appearance of withdrawal syndromes provides a powerful source of negative reinforcement, which stimulates compulsive drug-seeking behavior and relapse (Wise and Koob, 2014). The hypothesis of negative reinforcement is defended by Siegal and his compensatory response hypothesis, where he argues that drug-associated cues elicit a withdrawal-like state motivating ongoing drug use to achieve homeostasis.
Environmental cue and relapse
Besides, classic theory of addiction argues that drug-associated cue, such as environmental cue elicits ongoing drug use and relapse via negative reinforcement. Environmental stimuli exaggerate the incentive salience of time and space closely associated with the withdrawal state of addicts. Thus, environment associated with withdrawal working as a conditioned stimulus may elicit a conditioned withdrawal response, such as withdrawal symptoms. This argument is strongly defended by the experiment conducted by O’Brien (1977, p.195), where subjects under normal state are placed in a room compared with the subject under withdrawal state and subjects under normal state placed in the same room with a sound and a peppermint odour added. O’Brien surprisingly found out that subjects under withdrawal state experiencing a conditioned deceased in skin temperature compared with control group, which indicates that environmental cue may elicit conditioned withdrawal. According to the principle of negative reinforcement mentioned above, the avoidance of withdrawal response may result in a relapse to drug use. The relationship between withdrawal associated environmental cue and relapse is supported by the ‘wet dog’ experiment of Wikler (1967, p.16). Morphine-injected rats exhibit higher “wet dog” shake frequencies in their former “abstinence places” and opioid-seeking behaviour during 'relapse-testing' sessions compared with saline-injected normal rats over a prolonged period after termination of injection. Wikler suggests that environmental situations associated with acute withdrawal distress may motivate drug-seeking and relapse. The mechanism of how environmental stimuli may contribute to relapse is further investigated by Higgins (2008, p.59), who insists that humans will learn and maintain a new response under an aversive situation. Frequency of drug-seeking behaviour will increase in the presence of aversive environmental stimuli, which will eventually lead to ongoing drug use.
In conclusion, the development of drug addiction is a complex process that is evoked through physiological and psychological dependence on the drug. The mechanism of physiological dependence can be clarified by the study of dopaminergic rewarding system, while psychological dependence can be explained by the principle of instrumental conditioning, through either positive reinforcement or negative reinforcement. The understanding of drug addiction is crucial for potential treatment to cure substance use disorder.
Reference:
- Ghosh, S., Patel, A.H., Cousins, M. & Grasing, K. (1998). Different Effects of Opiate Withdrawal on Dopamine Turnover, Uptake, and Release in the Striatum and Nucleus Accumbens. Neurochemical Research, 23, 875–885. https://link.springer.com/article/10.1023/A:1022463029351
- Miguel, A. de Q. C., Yamauchi, R., Simões, V., Silva C. J. da, Laranjeira, R. R. (2015). From Theory to Treatment: Understanding Addiction from an Operant Behavioral Perspective. Journal of Modern Education Review, 5(8), 778-787. https://pdfs.semanticscholar.org/15da/3f90b6f779b6aade6156f2aed4809e16a721.pdf
- Wikler, A., M., D. & Pescor, F. T. (1967). Classical Conditioning of a Morphine Abstinence Phenomenon, Reinforcement of 0pioid-Drinking Behavior and 'Relapse' in Morphine-Addicted Rats. Psychopharmacology, 10, 255-284. https://link-springer-com.wwwproxy1.library.unsw.edu.au/content/pdf/10.1007/BF00401386.pdf
- Wise, R. A. & Koob, G. F. (2014). The Development and Maintaince of Drug Addiction. Neuropsychopharmacology, 39, 254-262. https://moodle.telt.unsw.edu.au/pluginfile.php/5315663/mod_resource/content/10/Ahmed_2012_The%20Science%20of%20making%20Durg-Addicted%20animals.pdf
- See, E. R. (2002). Neural substrates of conditioned-cued relapse to drug-seeking behavior. Pharmacology Biochemistry and Behavior, 71(3), 517-529. https://www-sciencedirect-com.wwwproxy1.library.unsw.edu.au/science/article/pii/S0091305701006827#BIB26
- Zangen, A. (2010). Novel perspectives on drug addiction and reward. Neroscience & Biobehavioral Reviews, 35(2), 127-128. https://www-sciencedirect-com.wwwproxy1.library.unsw.edu.au/science/article/pii/S0149763410000977
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