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 receptor by a pharmacologic antagonist bound to the receptor, effectively filling the electrical outlet so the plug cannot be inserted. Blockade studies use chemicals to stop a particular receptor from firing. Neuroimaging studies are used to provide images using brain- scanning technology to assess the effects of acute as well as long-term substance use on brain structure and functioning. A variety of brain-imaging techniques are used, such as the SPeCT, MeG, PeT, fMRI, and QeG. The SPeCT, or Single Photon emission Computerized Tomography, scan uses a radioisotope combined with a pharmaceutical that is injected into the patient to measure cerebral blood flow. The SPeCT scan measures brain receptor activity and involves a long exposure—up to six hours—after an injection to conduct the brain scan. With PeT (Positron emission Tomography) scans, a small amount of radioactive sugar is injected into a vein and a scanner is used to make computerized images that illuminate areas of increased glucose metabolism or receptor activity. It only requires a very short exposure. The fMRI (Functional Magnetic Resonance Imaging) scan compares the difference in the blood flow in the brain between conditions and activity like thinking, seeing, touching, and hearing to find regions of the brain that are associated with one task and not another. It involves a very short exposure and can be repeated as often as desired because there’s no radiation. The QeG (Quantitative electroencephalogram) scan is also known as a “brain map.” It’s a computer analysis of a brain wave signal that’s compared against a reference database. It’s often used for research studies. A MeG (Magnetoencephalography) scan is a technique for mapping brain activity by recording magnetic fields produced by electrical currents occurring naturally in the brain. Its applications include localizing regions of pathology before surgical removal, determining the functions of various parts of the brain, and neural feedback. To be an effective addiction therapist, you don’t have to completely understand all the subtleties of neuroanatomy and neurochemistry, but it is important to have a working familiarity with the parts and processes of the brain that are involved in the addiction cycle. Stimulation, either electrical or chemical, of the nucleus accumbens and ventral tegmental area (VTA) is intrinsically rewarding, while stimulation elsewhere in the brain is not. The reward can be interrupted by severing the nucleus accumbens/frontal cortex fibers or by using medication like dopamine blockers. This is how researchers came to know that blocking can interrupt natural reward pathways. There are patients in psychiatric hospitals, for example, who are on antipsychotic medications and often appear to lack emotion. Affect is the outward manifestation (facial expression, tone of voice, body language, etc.) of an emotion such as sadness, happiness, and excitement. Sometimes patients on certain psychiatric medications have very flat or unresponsive affect. Many of the psychiatric medications that block the neurochemistry that generates psychosis have an unfortunate side effect of also blocking the dopamine receptors. As a result, people on such medications may have difficulty experiencing pleasure, have a narrow emotional range, and have a very flat affect. However, without these medications, patients’ active psychosis returns. Dopamine is the primary transmitter that activates the brain’s reward center. It is the release and inhibition of reuptake/reabsorption of dopamine that generates experiences of pleasure and reward, and in turn, reinforces behavior. All mind- and mood-altering drugs ultimately act via the dopamine pathway. The longer someone uses alcohol or other drugs, the more of the substance(s) he or she needs to use in order to get the same high. This is the phenomenon of tolerance—a neuroadaptation wherein a substance no longer “works” and a higher dosage is required to achieve the same effect. Neuroadaptation refers to the process whereby the brain compensates for the presence of a chemical in the body so that it can continue to function normally. The brain is always attempting to maintain a state of balance or homeostasis. The way it works is that the first time you use drugs, especially a stimulant, but with any kind of psychoactive drug, you get a big boost in your mood, you feel euphoria from the substantial release of dopamine in the brain’s reward pathway. And then the next time you do it, you still feel good, but not as high as the first time, and the third time, not as high as the second time. And then eventually, you never get the same high anymore and you start feeling lower and lower. That’s neuroadaptation. Continued usage causes a gradual decrease in the number of receptors for the substance, along with a corresponding gradual decrease in the amount of available transmitters due to a feedback mechanism in the brain that seeks equilibrium. The brain squirts out a certain amount of dopamine when you have sex or eat chocolate, but if you’re getting a lot more dopamine stimulation from drugs (exogenous stimulation), the brain stops making its own dopamine (from endogenous production). That is because the feedback loop is informing the brain there is more than enough dopamine “on board” already. The fact that the brain makes less dopamine explains why, when people stop using crystal meth, cocaine, or other stimulants, they generally feel depressed and lethargic for up to several weeks or even months. Their brain has been depleted of dopamine and they don’t have enough to maintain a normal mood. It’s like trying to drive a car with an empty gas tank. The process goes like this: Continuing use creates an increased number of receptors and a decrease in the amount of available neurotransmitters. As the individual develops a tolerance to the drug, more of the drug is required to get the same high or rush. As the brain adapts to the presence of the drug through repetitive use, there is an increased need both for the drug and for greater quantities of it to maintain normalcy. These are the neurochemical dynamics of substance dependence. 7 James Olds and Peter Milner, “Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain,” Journal of Comparative and Physiological Psychology 47, vol. 6 (1954): 419–27. 8 Roy A. wise, “Brain reward circuitry: Insights from unsensed incentives,” Neuron 36 (2002): 229–40. 9 Michael A. Bozarth and Roy A. wise, “Toxicity associated with long-term intravenous heroin and cocaine self-administration in the rat,” Journal of the American Medical Association 254, vol. 1 (1985): 81–3. This blog post is an excerpt from The therapist’s Guide to Addiction Medicine – A Handbook for Addiction Counselors and Therapists – by Barry Solof, MD, FASAM; Published by Central Recovery Press (CRP).