Dopamine is an important catecholamine neurotransmitter in the human brain. It is involved in motor function in the peripheral nervous system and cognition in the prefrontal cortex.
Addiction and Dopamine
Dopamine is also a part of reward pathways in the brain—it is responsible for that flood of good feelings you get in response to positive reinforcement. This is why for several decades it has been viewed as the primary neurotransmitter involved in addiction.
Drug addiction is a chronic brain disorder that involves:
- Compulsion to seek and take a drug
- Loss of control in limiting drug intake
- A negative emotional state (anxiety, irritability, or depression) when access to the drug is prevented [1]
Drug Addiction in the U.S.
It is a disorder that affects a large portion of the United States population.
- 4 million people are dependent on illicit drugs
- 18 million people are dependent on alcohol
- 9 million people are currently tobacco users [1]
Is Disordered Dopamine to Blame for All This Addiction?
For a long time, that was the consensus in the scientific community.
It began in the 1970’s when researchers found the mesolimbic dopamine pathway in the brains of rats to be activated by stimulant drugs [1,2,3]. Further research found dopamine to be released in rats’ brains in response to other drugs of abuse, not just stimulants [2].
It was a breakthrough finding and seemed to implicate dopamine as the main neurotransmitter involved in the reward pathways for drug intoxication.
This research led to generalized theory of addiction which proposed that drugs of abuse caused dopamine to be released in the brain, while non-addictive substances did not [2].
Recent Research on Addiction and Dopamine
However, we are now finding that drug addiction is a more neurologically complicated disorder than previously thought. Different drugs affect our brain chemistry in different ways.
The reward pathways for psychostimulants are in fact dependent upon dopaminergic transmission, but dopamine does not seem to be as critical for the positive reinforcement of other addictive drugs [1,2]. There are also other neurotransmitters that modulate mesolimbic dopamine activity involved in drug consumption [3].
Studies have found that heroin administration showed little to no effect on dopamine levels in the striatum (an important part of the reward system in the mesolimbic pathway) [2]. This is contrary to the dopamine hypothesis of addiction, because as we know, heroin is an extremely addictive drug.
GABA and Addiction
These results can be explained by the observation that opiates have reward effects which are independent of dopamine [3]. This hypothesis is supported by studies that show morphine and heroin use can be modified by specifically blocking the actions of GABA in the mesolimbic pathway [3].
THC and GABA Function
THC, the psychoactive component of cannabis, also has been shown to have only a small effect on striatal dopamine levels [2].
THC manipulates the endocannabinoid system in the brain primarily by activation of the CB1 receptor. CB1 is an abundant neuromodulator in the hippocampus, the area of the brain important in forming long term memories [4].
CB1 receptors in the hippocampus are localized to GABA neurons, suggesting that endocannabinoids regulate GABA release. Exogenous cannabinoid molecules from marijuana use suppress GABA inhibition which may lead to impaired cognition and memory. [4]
Serotonin, Glutamate, and GABA Function in Alcohol Abuse
Alcohol, another commonly abused drug, initiates complex neurotransmitter interactions in the brain as well. Serotonergic, glutamatergic, and GABAergic systems have all been found to be active in alcohol intoxication, explaining its wide variety of physiological effects [3].
Decreased serotonergic transmission has been found to occur during the withdrawal stages from alcohol as well as all major drugs of abuse [1].
Factors in Addiction Besides Dopamine
There are certainly more factors involved in addiction than simply increased dopamine.
In fact, contrary to the dopamine hypothesis of addiction, some studies which followed addiction within families suggest that higher availability (more receptors and more release) of dopamine in the brain may actually be neuroprotective for individuals who are genetically predisposed to addictive behaviors [2].
Drug addiction is a complicated disorder that involves not only reward and intoxication, but drug seeking behaviors, genetic, and epigenetic factors that influence a drug user’s actions. It is important to remember that human behaviors are more complex than the animal models on which most drug research is based.
It appears as though the dopamine addiction hypothesis should be reevaluated in order to better understand the way in which drugs of abuse affect the human brain. New insight could provide new treatment options and allow practitioners to more easily heal their patients with addiction.
References
- Koob GF & Volkow ND. (2010). Neurocircuitry of Addiction. Neuropsychopharmacology, 35(1), 217–238.
- Nutt DJ, Lingford-Hughes A, Erritzoe D, et. al. (2015). The dopamine theory of addiction: 40 years of highs and lows. Nature Reviews Neuroscience, 16, 305-310.
- Tomkins DM & Sellers EM. Addiction and the Brain: neurotransmitters in the cause and treatment of drug dependence. Canadian Medical Association Journal, 164(4), 817-821.
- Wilson RI & Nicoll RA. (2002). Endocannabinoid Signaling in the Brain. Science, 296, 678-682
Clinical Contributor
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