11.7: Theories of Addiction

Non-human models of addiction

One of the most instructive non-human animal models of drug use disorder is called self-administration. In a self-administration experiment, the subject (usually a monkey, rat, or mouse) gets a surgical implantation of an indwelling intravenous tube that is connected to a pump. Then, the subject is put into an operant conditioning chamber. When they press the lever or poke their nose into a hole, the pump triggers, resulting in an infusion of drug directly into the bloodstream.

This experimental paradigm closely mimics human drug seeking behavior. For example, rats and mice will very quickly learn to press on the levers for intravenous infusions of cocaine and morphine. Many of them will give themselves drugs even despite severe adverse consequences, such as enduring foot shock - arguably similar to human behavioral patterns where drug users may do all kinds of behaviors for access to drug. Monkeys, if given the option to self administer for cocaine, must be restricted in the amount of drug they receive: if given unrestricted access, they give themselves so much cocaine that they have seizures and die.

A second experimental test created to study drug misuse is called conditioned place preference (CPP). A CPP test works on the principle that animals learn to associate certain environments with positive feelings, and will prefer to spend significantly more time in those environments. To conduct CPP, a three-room testing chamber is used. This experimental chamber has two large rooms, each with characteristics that are unique to that room. For example, one room may have mesh flooring with dark-colored walls, while the other room may have woodchip flooring with light-colored walls. The two rooms are connected by a smaller, neutral room, and the rooms can be isolated from another by means of a dividing door. To conduct CPP, an animal will be given the drug of interest, then placed into one of the two rooms, where they are free to explore the room, but cannot leave. As a control, at a different time, they will be injected with an innocuous solution and placed into the other room. On test day, the animal will be put into the neutral middle room, and given the opportunity to move freely between the two chambers. If the animal developed positive associations with the room where they experienced the drug effect, then they will choose to spend significantly more time in that room. On the other hand, if they experienced negative feelings associated with that room, they will avoid being in the room. Whereas self-administration assesses “drug seeking,” CPP measures “drug liking.”

Below are three major biology-driven hypotheses that have been proposed to explain drug addiction. It’s important to note that none of them tell the complete story - otherwise drug addiction will have already been cured! Also, these theories are not mutually exclusive from one another. A likely answer to curing addiction probably incorporates some combination of these approaches in addition to societal-level policy changes.

The “hedonia hypothesis”

What drives drug users to behave in the way they do? One of the earlier theories put forward to explain addiction is the hedonia hypothesis proposed in the late 1970s by Roy Wise. The hedonia hypothesis hinges on the assumption that dopamine is the “pleasure neurotransmitter,” and that any substance or behavior that increases dopamine will be desirable. The theory is supported by some behavioral data. For example, using microdialysis, it was found that dopamine release by the mesolimbic pathway increases in the presence of many drugs. Additionally, administration of dopamine antagonists are able to block some drug taking behavior. This dopamine-centric approach to drug use disorder was so influential that pharmaceutical companies, while developing novel antidepressants, quickly dismissed drugs that increased dopamine out of fear of the risk of addiction potential.

Despite the attractiveness of the straightforward “pleasure neurotransmitter” model, the hedonia hypothesis does not give us the whole picture. For one, dopamine release at the mesolimbic pathway is only notable for psychostimulant drugs, such as cocaine and methamphetamine. But there are plenty of stimulants that still produce the significant overflow of dopamine without causing any rewarding sensation. Furthermore, if dopamine is the signal that mediates the positive hedonic feelings, one might predict that by blocking dopamine receptors chronically, you can also prevent long-term cocaine addiction, but this therapeutic strategy isn’t very useful. Many of the most popular misconceptions about dopamine that you frequently see in the media take this early hypothesis as the truth. It even was featured as the cover of a 1997 Time magazine. That same year in an interview with the original proponent of the hedonia hypothesis published in Science, Roy Wise agreed with recent results that his model was incomplete.

The incentive sensitization model

A more recent theory to explain drug addiction is a model developed by researchers from the University of Michigan, Terry Robinson and Kent Berridge. Under their model of drug use, initially a person takes a drug because they like the positive, euphoria-producing side effects of the substance. But after chronic exposure to the substance, the person becomes fixated on obtaining the drug rather than how the drug makes them feel. At this point, they continue to use the drug even though they no longer enjoy the drug to the same degree that they once did. Instead of “liking” the drug, the user fixates on “wanting” the drug.

The incentive sensitization model suggests that the drug-exposed brain develops an increased sensitivity to drugs, but also more importantly, drug-related cues. Pavlovian learning takes place when a user takes a drug. Each drug has an associated set of cues, and re-exposure to those cues can trigger relapse. Over repeated pairings, those cues trigger a progressively stronger response.

Their model accounts for why it is difficult to remain abstinent from an addictive drug for long durations of time. Despite a decrease in drug seeking behaviors, many users eventually relapse, or return to the previous destructive pattern of drug use. One phenomenon that makes staying drug free difficult is the observation that prolonged abstinence can increase the intensity of drug cravings. This is called incubation of craving, and is seen with several different classes of drugs, notably, nicotine.

The Brain Disease Model of Addiction (BDMA)

Much of our current understanding of addiction is based on the principles that repeated drug use leads to biological changes in the brain that resemble aberrant learning. This model for drug addiction is called the Brain Disease Model of Addiction. Genetics has a strong influence on the likelihood that someone develops a disease, and addiction is no different. Inherent risk-taking behaviors, magnitude of a drug effect, and risk of relapse are all modified by genetics.

One of the major implications of the BDMA is that compulsive drug use and seeking is not a choice that a person makes. Drug users are not the way they are because of some poor moral guidance or a weakness of willpower. They compulsively seek drug because of some underlying circuitry of their brain that makes cessation difficult. One substantial accomplishment of the BDMA is that public policy has adjusted to increase access to mental health resources for addicts to help cover the financial challenges of recovery programs (Mental Health Parity and Addiction Equity Act of 2008), and to improve the outcomes of nonviolent drug offenders as they reintegrate with society outside of prisons.

The BDMA is not without fault, however. The major criticism of this framework to explain compulsive drug use is that most people stop their addictive use patterns by themselves spontaneously without any treatment. Another harm of the BDMA is that it puts heavy emphasis on biochemical therapies rather than on a public policy approach to drug addiction treatment. Lastly, the BDMA has not produced a successful therapeutic strategy to help with substance use disorder.