The effects of addictive drugs on our reward system and the journey towards addiction

By Themis Halka 

Drug consumption is a major problem in today’s societies due to its relatively easy availability and strong tendency to lead to addiction. The effects of drugs on the brain have been a central field of study for many years, with scientists trying to understand the changes occurring in the brain’s structure upon their influence. The implication of the ventral tegmental area and nucleus accumbens in particular have been shown to play a role in the process. 

There are many addictive drugs which can be classified according to their effect on our organism. Stimulants, like cocaine, MDMA or caffeine, increase the heart rate and stimulate the nervous system, as opposed to depressants and opioids, including alcohol, morphine or heroin that inhibit it. Hallucinogens like LSD cause hallucinations and distorted perceptions (National Institute of Drug Abuse, 2021). Yet, however different these drugs might be, evidence shows that all addictive drugs, with the exception of LSD and mescaline-like hallucinogens, activate the reward circuitry of our brain (Gardner, 2011). 

Our brain’s reward system is extremely complex, and far from being entirely understood. A central part of this circuitry is the mesolimbic pathway, consisting of the ventral tegmental area (VTA), the nucleus accumbens (NAc), and other regions like the amygdala, the prefrontal cortex and the hippocampus (Pariyadath, 2016). The VTA and NAc are particularly important in drug action. This complex circuitry is responsible for the pleasure we gain from an experience, which is remembered through the involvement of the different regions mentioned above, the amygdala for example being concerned with retaining the emotions from the pleasurable experience (Gardner et al., 2011). A basic, partial and largely simplified description of the reward system would mention the activation of the VTA and firing of its dopamine neurons, which represent 60-65% of VTA’s neurons (Cooper et al., 2017). These neurons activate the other regions of the reward system (NAc, amygdala) via the release of the neurotransmitter dopamine onto the receptors of their constituting neurons (Adinoff, 2004). 

A great number of studies have been led on drugs and their effect on the brain, which revealed that all known addictive drugs affecting the reward system act by increasing the release of dopamine into the NAc, either directly or indirectly. Consequently, blocking the action of dopamine has shown to block many behavioural effects of drugs (Anderson et al., 2004). If all drugs behave like functional dopamine agonists, their target can differ. Some drugs act on the dopamine neurons from the VTA, like cocaine, which blocks the synaptic dopamine transporter responsible for the reuptake of dopamine after its release in the synaptic cleft. Amphetamines, on the other hand, mainly increase the release of dopamine from the neuron’s vesicles (Adinoff, 2004), whilst opiates suppress inhibitory inputs onto dopamine neurons (Oliva et al., 2016). Therefore, these drugs cause the increase of dopamine levels at the synapse. Other drugs like caffeine or nicotine affect the neurons from the NAc, principally acting on the receptors located on their cell bodies that transmit the signals along the pathway (Adinoff, 2004). Therefore, the great majority of addictive drugs affect the action of dopamine within the mesolimbic pathway. 

The increased levels of dopamine induced by drugs fire up the reward system, making the user ‘high’ (Gardner, 2011). As these drugs lead to increasing activation of the reward system, which is ‘hijacked’ compared to normal conditions, users want to repeat the experience after having tried the drug. It leads in some cases to the establishment of an addictive state when the user regularly seeks the drug (here we talk about addiction, which is different from physical dependence to a drug) (Adinoff, 2004). Drug addiction progresses as the user’s consumption is not reward-driven but evolves to a habit-driven, drug-seeking behaviour; the occasional recreational use becomes impulsive and finally habitual compulsive (Gardner, 2011).

As we saw earlier, drugs hijack the reward system by firing dopamine neurons from the VTA. In addition, it is thought that the activation of dopamine neurons is also linked to the importance of the event: the more surprising the experience, the stronger the activation of the reward system (Korpi et al., 2015). This is important as the reward system is directly linked to memory, regions like the amygdala or hippocampus being involved in remembering the pleasurable experience. A strong and long-lasting stimulation of the reward circuitry would potentially lead to an enhanced memorisation of the experience, creating a motivational behaviour towards the reiteration of the experience. 

Numerous studies have shown drug addiction to be associated with changes in structure and plasticity of the reward circuitry; there are neurophysiological changes involved in drug addiction, which doesn’t only have psychological causes (Golden et al., 2012).

The brain, as always, aims to maintain homeostasis within the body, which means it has to adapt to events, like repeated drug consumption. Neuroplasticity enables the modification of pathways and structures in reaction to events. Following absorption of a drug, changes occur in our brain. If a drug is repeatedly consumed, lasting changes will be induced, progressively leading to the need for the user to keep consuming the drug. Various types of drugs cause different changes, but the VTA has been shown to be largely influenced by the majority of them (Korpi et al., 2015). Studies are currently being led in order to determine if changes in neuroplasticity caused by the intake of one type of drug could increase the probability of falling into other drug addictions. Drug intake by adolescents in particular is a great concern, as studies suggest that neuroplasticity would be more malleable in adolescents, who then might be subjected to enhanced addiction behaviours (Korpi et al., 2015). In the USA, in 2014, it was estimated that 5% of the 12-17 years old were concerned with alcohol or illicit drug abuse or addiction (SAMHSA, 2014).  

Drug addiction is a serious problem that has impacted many lives. Intense research is currently led, using the knowledge acquired on the action of each drug on our nervous system to try countering their effect, remediating neuroplasticity changes. Here the focus lied on the VTA and NAc as they are primarily impacted by drugs, however many other regions of the reward system and brain are also affected by drug intake, and current research aims to get a deeper understanding on their implication, which might help to fight drug addiction. 

References :

National Institute on Drug Abuse. 2021. Commonly Used Drugs Charts | National Institute on Drug Abuse. Available at: https://www.drugabuse.gov/drug-topics/commonly-used-drugs-charts [Accessed 2 March 2021].

Gardner EL. Addiction and brain reward and antireward pathways. Adv Psychosom Med. 2011;30:22-60. doi:10.1159/000324065 

Pariyadath V., Gowin J., Stein E. Resting state functional connectivity analysis for addiction medicine: From individual loci to complex networks. Progress in Brain Research

2016;224:155-173.

Cooper S, Robison AJ, Mazei-Robison MS. Reward Circuitry in Addiction. Neurotherapeutics. 2017;14(3):687-697. doi:10.1007/s13311-017-0525-z

Adinoff B. Neurobiologic processes in drug reward and addiction. Harv Rev Psychiatry. 2004;12(6):305-320. doi:10.1080/10673220490910844

Anderson SM, Pierce RC. Cocaine-induced alterations in dopamine receptor signaling: implications for reinforcement and reinstatement. Pharmacol Ther. 2005;106:389–403. doi: 10.1016/j.pharmthera.2004.12.004.

Oliva I, Wanat MJ. Ventral Tegmental Area Afferents and Drug-Dependent Behaviors. Front Psychiatry. 2016;7:30. doi:10.3389/fpsyt.2016.00030

Korpi ER, den Hollander B, Farooq U, Vashchinkina E, Rajkumar R, Nutt DJ, Hyytiä P, Dawe GS. Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse. Pharmacol Rev. 2015 Oct;67(4):872-1004. doi: 10.1124/pr.115.010967

Golden SA, Russo SJ. Mechanisms of psychostimulant-induced structural plasticity. Cold Spring Harb Perspect Med 2012;2.

SAMHSA: Substance Abuse and Mental Heath Services Administration, Center for Behavioral Health Stistics and Quality. September 4, 2014. The NSDUH Report: Substance Use and Mental Health Estimates from 2013 National Survey on Drug Use and Health: Overview of Findings,Substance Abuse and Mental Health Services Administration, Rockville, MD.

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