Category Archives: Substance Abuse

What Is the Role of Dopamine in Alcoholism?

Alcohol is one of the most widely used psychoactive substances in the world. Alcohol-induced changes in brain functions are key contributing factors to acute intoxication, long-term misuse and the development alcohol use disorder (AUD) or dependence. AUD is a chronic relapsing brain disease characterized by compulsive alcohol use, loss of control over alcohol intake and a negative emotional state when not drinking alcohol. Extensive research has been done on the role of dopamine in alcohol dependence, as well as other substance and behavioral addictions.

What Is Dopamine?

Dopamine is a brain chemical (neurotransmitter) released by brain cells (neurons). Often called the “feel-good” chemical, dopamine is released when people feel pleasure. Neurotransmitters transmit signals from the brain to the body by passing across small gaps (synapses) between each neuron, thereby controlling a multitude of body functions. As the primary neurotransmitter in the brain’s reward center, dopamine modulates physiological functions including food consumption, movement, sleep, learning, mood, memory, sexual behavior and attention. Unbalanced dopamine levels (low or high) are implicated in many conditions, including depression and Parkinson’s disease.

Dopamine is the primary neurotransmitter in the brain’s reward system, which is part of the limbic system. The dopamine system includes the nigrostriatal, mesolimbic and tuberoinfundibular pathways. Dopamine is mainly produced in the substantia nigra area of the brain, projected along the nigrostriatal pathways and stored in the striatum. Five subtypes of dopamine receptors have been identified and cloned. All of these function both individually and interactively as G-protein coupled receptors.

What Is the Dopamine-Alcoholism Connection?

The reward system is the target of psychoactive substances including alcohol, cocaine, amphetamine and opioids. Electrophysiological studies found acute alcohol intake can increase dopamine release in the substantia nigra and ventral tegmental area (VTA). Levels decrease during alcohol withdrawal and are restored after alcohol intake is resumed. Research also suggests the amygdala, an area of the brain in the reward circuitry, plays a central role in the alcohol-induced effects on the brain. Other studies have found alcohol can also indirectly increase dopamine levels by interacting with gamma-Aminobutyric acid (GABA) neurons and opioid receptors in the nucleus accumbens.

Alcohol and Dopamine Research

Basic studies have demonstrated optimal levels of prefrontal cortical dopamine are critical to functions such as working memory, attention, inhibitory control and risk/reward decisions. All of these are impaired in addictive disorders such as alcoholism. Decreased dopamine transmission in the mesolimbic regions, such as the VTA and medial temporal lobe, likely contributes to the psychological side effects and decreased reward sensitivity in alcohol dependent individuals.

A 2014 study used amphetamine and positron emission tomography (PET) to measure and compare cortical dopamine transmission in 21 recently abstinent alcoholics and 21 healthy controls aged 18-40. None of the subjects had any other current or past substance disorder other than nicotine. Cortical dopamine in healthy controls and alcohol dependent subjects increased by 513-798% and 0-228% respectively, following the same dose of amphetamine. This was the first study to clearly demonstrate the existence of decreased dopamine transmission in the cortex in alcoholism. Less dopamine in the prefrontal cortex, which governs executive functions, is important because it could impair an alcohol-dependent individual’s ability to learn and utilize informational/behavioral strategies critical to relapse prevention.

2016 study suggests when an alcoholic stops drinking, the brain’s ability to use dopamine changes, altering the way the reward system is wired. The study analyzed a specific type of dopamine receptor called D1 – dopamine binds to these receptors on the membranes of neuronal cells, causing neurons to become excited. Using sample postmortem brain tissue from deceased alcoholics, researchers found significantly decreased striatal D1 receptor and dopamine transporter binding sites. Fewer D1 receptors make the brain less responsive to dopamine, causing an individual to struggle in order to feel the same pleasure from alcohol others may experience. Brain tissue showed no reduction in D2 receptor sites, which bind with dopamine in order to inhibit, rather than excite neurons. The combination of these characteristics ultimately interfere with the brain’s ability to use dopamine, subsequently inhibiting the ability to feel pleasure, which potentially leads to tolerance and relapse.

The second part of the study utilized rats to determine the mechanisms leading to altered dopamine activity. Researchers tracked dopamine levels in the brains of alcohol-dependent rats after they were denied alcohol for several weeks. Dopamine levels dropped during the first six days, confirming the existing theory acute alcohol withdrawal is characterized by a hypodopaminergic state. While the availability of dopamine receptor sites and transporter sites were normal during this period, after three weeks, dopamine levels become elevated and the rats continued to exhibit signs of alcohol craving. The number of available receptor and transporter sites plummeted at this stage and the rats’ brains resembled those of the deceased alcoholic humans.

The authors concluded while acute alcohol withdrawal may be associated with a hypodopaminergic state, prolonged abstinence leads to a hyperdopaminergic state, in which dopamine levels are higher than normal. The hyperdopaminergic state is associated with increased motor activity and augmented alcohol seeking, however, both states reflect a dysfunctional reward system and may increase the risk of relapse.

Potential Alcoholism Treatment Targeting Dopamine

It has been well established the VTA plays an important role in mediating reward and reinforcement in drugs of abuse, as well as food. The important connection between the VTA and dopamine neurotransmission has been the subject of alcohol studies in animals for 30 years. Researchers hope a better understanding of the mechanisms of adaptation to alcohol after chronic use and the sequence of molecular events leading from reward-seeking to compulsive use may lead to more efficacious therapeutic interventions.

Two Swedish studies by the same research team demonstrated the potential efficacy of the dopamine stabilizer OSU6162 for the treatment of alcoholism. In the first study, half the participants were treated with OSU6162 and half with placebo for two weeks, after which both groups were exposed to potential situations that could trigger alcohol craving. The OSU6162 group experienced less alcohol craving after drinking one glass of an alcoholic beverage and less enjoyment. The group that responded best to OSU6162 consisted of individuals with the worst impulse control and the greatest risk of relapse.

In the other study, rats that voluntarily consumed alcohol for almost a year had lower levels of dopamine in their brain reward system than the alcohol-naïve control group. When the “alcohol rats” were treated with OSU6162, the substance counteracted the low concentrations of dopamine. Although far more studies are needed before this treatment can be marketed, researchers believe OSU6162 can reduce alcohol craving in alcohol-dependent individuals by returning diminished levels of dopamine in their brain reward systems to normal.

A 2018 study confirmed the efficacy of OSU6162 in improving motor impulsivity in both alcohol and alcohol-naïve rats and its possible therapeutic use for AUD. Pre-treatment with OSU6162 prior to the rats’ 10-week exposure to alcohol prevented relapse-like drinking behavior after a forced period of abstinence. The results indicate improved motor impulse control might be one mechanism underlying OSU6162’s ability to lessen alcohol-provoked behaviors.

How Heroin Wrecks Your Body and Your Brain

Heroin Addiction Effects on the Brain Heroin is one of the most addictive of all drugs, including both illicit and legal, controlled substances. With long-term use, heroin can cause a number of serious health problems, up to and including death from an accidental overdose. If someone you care about is using heroin, it’s never too late to help rescue her from her addiction. Help her see the problems that heroin is creating in her life and what it will do to both her mind and her body over time. The reality is scary, but anyone struggling with addiction to heroin can get treatment and begin to reverse the ill effects.

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The Rate of Americans in the Workforce Abusing Drugs or Alcohol

Businessman with Substance Abuse Disorder

A common misconception about addiction is that those abusing drugs or alcohol must be degenerate, jobless and most likely homeless. Though the term “addict” implies multiple negative stereotypes, not everyone fits the mold of what an addicted person is assumed to look and act like. In fact, a 2007 study from the National Institute on Alcohol Abuse and Alcoholism discovered that only 9% of alcoholics seem to fit the “chronic severe” stereotype of having higher rates of psychiatric disorders and criminality.
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