05 Jun Potential Neurotransmitter-Blocking Treatment for Drug Addiction
Drug addiction researchers have long noted the fact that people exposed to a drug of abuse frequently exhibit a high degree of willingness to seek that drug out in the future. The specific degree of willingness displayed by any given individual helps determine that individual’s risks for the eventual development of a drug addiction. According to a review released in 2011 by the National Institute on Drug Abuse, much of the drive behind drug-seeking behavior stems from the effects of a neurotransmitting chemical in the brain called orexin or hypocretin. In the future, doctors may be able to reduce the risks for drug addiction and relapse with the help of therapies that block the effects of orexin in susceptible individuals.
Orexin is produced by roughly 10,000 to 20,000 nerve cells called neurons, located in a part of the brain known as the hypothalamus. In some contexts, it functions as a neurotransmitter by helping to facilitate the neuron-to-neuron communication that forms the core of the brain’s basic functionality; in other contexts, it functions as a hormone by sending out chemical messages that affect a variety of different types of cells throughout the body. Specific aspects of the body’s normal processes regulated to some degree by orexin include your hunger levels, your ability to react to stimulating changes in your local environment, and your overall degree of wakefulness. In fact, wakefulness is so closely tied to orexin that people with damage in their orexin-producing neurons commonly develop a form of the sleep disorder called narcolepsy.
In order for orexin to achieve its effects inside the brain, molecules of the neurotransmitter must chemically activate sites on the surfaces of various neurons called orexin-1 receptors. In addition to its other effects, this receptor activation produces an increase in the brain’s levels of another neurotransmitter, called dopamine, in an area of the brain known as the limbic system. In turn, the heightened presence of dopamine in this system produces subjective feelings of pleasure in the individual. In the context of orexin’s effects on drug-seeking behavior, this is important because the vast majority of addictive drugs also produce their basic brain effects by boosting dopamine levels inside the limbic system (although they trigger much greater dopamine increases than orexin).
Effects on Drug-Seeking Behaviors
In 2006, researchers from the University of California, San Francisco and the University of British Columbia conducted animal experiments designed to determine orexin’s role in the persistent drive to seek out drugs. At the beginning of their study, the researchers injected a group of rats with a manmade substance, called SB334867, which blocks orexin’s ability to access the brain’s orexin receptors. Along with a second group of rats with unblocked orexin receptors, this group of animals was given a single dose of cocaine. When later presented with an opportunity to seek out more cocaine, the group of rats with blocked orexin receptors gave up their efforts at drug procurement fairly quickly. However, the group with the normal orexin receptors continued to seek out a new drug source for roughly twice as long. From these findings, the researchers concluded that orexin’s effects play a significant role in an individual’s willingness to seek out further drug use after an initial drug experience. As noted previously, a strong willingness to seek out drugs is a major factor in the later development of drug addiction.
In two additional studies, researchers from the Medical University of South Carolina examined orexin’s role in the potential for a relapse in recovering drug addicts. These researchers also used two groups of rats, one of which had its orexin receptors blocked by SB334867. Both of these groups of animals were regularly exposed to cocaine in a specific environment, then removed from that environment and allowed to go through drug withdrawal. Later, they were reintroduced to the same environment where cocaine use had occurred, but did not receive renewed cocaine access. The rats with blocked orexin receptors did not display strong signs of recurring drug-seeking behaviors. However, the rats with unblocked orexin receptors did display strong drug-seeking behaviors and a willingness to return to drug use (i.e., a willingness to relapse).
Potential for a New Treatment
Although the studies referenced here involved rats rather than humans, they likely also apply to human beings. This is true because rats and humans have highly similar orexin molecules and orexin receptors in their brains. In the future, researchers may be able to develop a drug for humans that produces the same orexin-blocking effects as the SB334867 used on rats. If such a development occurs, doctors may be able to prevent the onset of addiction in current drug users, or prevent the onset of a relapse in addicted former drug users.
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