www.nida.nih.gov Used courtesy of R.D. Schwartz-Bloom & G.G. de Nunez
Most mind- and mood-altering drugs generate high levels of pleasure in the reward center by increasing dopamine levels. If the nervous system can be considered a highway that transports people mentally and emotionally, dopamine functions as the car that travels the highway of the nervous system. If you’re driving and press the gas pedal to the floor, you’re going to go really fast. But if you keep your foot on the accelerator, not only are you at great risk of getting into an accident, but you will eventually run out of gas—and that’s what happens with the repetitive use of substances that takes place in addiction.
Almost all drugs of abuse exert an effect on dopamine levels, causing a release of and/or preventing reuptake of this neurotransmitter. Interestingly, in addiction treatment we don’t see too many people come in because they’re addicted to LSD and other hallucinogens because these drugs affect serotonin though not dopamine levels. Stimulants such as cocaine and crystal meth cause the biggest increase in dopamine levels, effectively flooding the brain with it. Figure 3 shows dopamine flooding the synapse between neurons subsequent to the ingestion of cocaine. Not only does cocaine stimulate the release of extraordinary amounts of dopamine, but it also inhibits the reuptake of that dopamine, effectively blocking it from entering the next neuron. As a result the dopamine remains in the synaptic space much longer. This is what creates the incredibly intense high users describe.
FIGURE 3
www.nida.nih.gov Used courtesy of R.D. Schwartz-Bloom & G.G. de Nunez
However, the massive release of dopamine also means that the brain’s supply of it is rapidly depleted, precipitating an equally intense crash as the car runs out of gas.
Cannabinoids are neurotransmitters linked to pain modulation. Cannabinoid receptors share some properties with opiate receptors in that they are involved with nociception, the ability to feel pain. So the cannabinoid receptors are anti-pain receptors and their activation can also cause sedation. Cannabinoid receptors are activated by cannabinoids, generated naturally inside the body (endocannabinoids) or introduced into the body externally as cannabis or a related synthetic compound. When people smoke marijuana, they experience sedation.
The GABA system is where the depressants or “downers” come into play. GABA is the chief inhibitory neurotransmitter, so it is involved with alcohol and tranquilizer use. Use of alcohol, Xanax, and Valium makes the individual feel calmer, sleepier, and less anxious via activation of the GABA receptor system. And GABA binds to the sub-receptors and activates secondary messengers, which have an effect on dopamine as well. Glutamate is the principal excitatory neurotransmitter, but it is also involved in the regulation of learning and memory. It binds to the NMDA receptor and is implicated in many of the excitatory chemical reactions.
Neurotransmitters can be viewed as the electrical plugs and receptors as the electrical outlets that neurotransmitters fit into. Every cell in our body has many types of receptors on it. Receptors allow substances, such as dopamine, to enter cells. Without receptors a substance can have no effect because it cannot enter the cell. An agonist is a substance that binds to a specific receptor and triggers a response in the cell. Agonists can be drugs, medications, or naturally occurring chemicals that interact with nerve cell receptors to stimulate drug actions or effects. For example, if you sprain your ankle, your body is going to release natural cannabinoids and natural opioids (known as endorphins) that bind to their specific receptors and decrease pain.
All neurotransmitters—serotonin, dopamine, glutamate, endorphins, cannabinoids, etc.—have specific receptors in the brain that they plug into. For example, opioid pain medications bind to endorphin receptors in the brain and their effects are limited by the number of receptors present. The neurotransmitter receptors that are involved in addiction are
There are three major opioid receptors. The mu receptor is the key to opiate addiction. Some of the other receptors have more to do with pain, but the mu receptor, when it’s ignited, triggers the most dramatic psychoactive response. When opioids attach to the mu receptors, dopamine is released, causing pleasurable feelings to be produced. As opioids leave the receptors, pleasurable feelings fade and withdrawal symptoms (and possibly cravings) begin.
The structures in the brain that these neurotransmitters activate and that are involved in the addiction cycle are the prefrontal cortex, the nucleus accumbens, and the ventral tegmental area (VTA). The reward pathway connects the VTA to both the nucleus accumbens and the prefrontal cortex via this pathway. The neurons of the VTA release dopamine in the nucleus accumbens and in the prefrontal cortex.
In 1953, experiments by James Olds and Peter Milner revealed first glimpses of the neuroanatomy of the reward pathway of the brain. They discovered that rats would press a bar to receive a pulse of electricity through an electrode implanted in a specific area of the brain. This electrical stimulation of the reward pathway proved to be so powerfully self-reinforcing that rats would press the bar at rapid rates for fifteen to twenty hours until exhausted, all the while ignoring food, water, and in the case of mothers their pups, in order to continue to receive the stimulation.7
Subsequent research on how drugs activate the reward pathway demonstrated that rats and monkeys will compulsively self-inject cocaine intravenously, to the neglect of food, water, and mating, even with females in heat. When access to the drug was unlimited, they would self-inject until they died. Using cocaine to stimulate the reward pathway in the brain became the animals’ highest priority in life—everything else took a backseat.8, 9
There is a substantial body of research, including stimulation studies, ablation studies, blockade studies, and neuroimaging studies that support the influence of the reward pathway in determining behavior. Stimulation studies involve exciting or arousing the test animal by placing a lead (electrode) in the reward center of the brain. Ablation means surgical destruction of anatomy of the reward pathway. When the anatomical structures of the reward pathway are taken “offline,” test animals will no longer respond to cocaine or other drugs because they can no longer stimulate the part of the brain that evokes pleasure. Pharmacological blockade involves blocking the effect of a neurotransmitter at a cell-surface
