Snorted, smoked, or injected, cocaine rapidly enters the bloodstream and penetrates the brain. The drug achieves its main immediate psychological effect—the high—by causing a buildup of the neurochemical dopamine.
Dopamine acts as a pacesetter for many nerve cells throughout the brain. At every moment of our lives, dopamine is responsible for keeping those cells operating at the appropriate levels of activity to accomplish our needs and aims. Whenever we need to mobilize our muscles or mind to work harder or faster, dopamine drives some of the involved brain cells to step up to the challenge.
Dopamine originates in a set of brain cells, called dopaminergic (dopamine-making) cells, that manufacture dopamine molecules and launch them into their surroundings. Some of the free-floating dopamine molecules latch onto receptor proteins on neighboring (receiving) cells. Once attached, the dopamine stimulates the receptors to alter electrical impulses in the receiving cells and thereby alter the cells’ function.
The more dopamine molecules come into contact with receptors, the more the electrical properties of the receiving cells are altered. To keep the receiving cells in each brain region functioning at appropriate intensities for current demands—neither too high nor too low—the dopaminergic cells continually increase and decrease the number of dopamine molecules they launch. They further regulate the amount of dopamine available to stimulate the receptors by pulling some previously released dopamine molecules back into themselves.
Cocaine interferes with this latter control mechanism: It ties up the dopamine transporter, a protein that the dopaminergic cells use to retrieve dopamine molecules from their surroundings. As a result, with cocaine on board, dopamine molecules that otherwise would be picked up remain in action. Dopamine builds up and overactivates the receiving cells.
Although cocaine also inhibits the transporters for other neurotransmitter chemicals (norepinephrine and serotonin), its actions on the dopamine system are generally thought to be most important. To understand the powerful nature of cocaine’s actions, it is helpful to realize that dopamine pathways in the brain are very old in evolutionary terms. Early rudiments are found in worms and flies, which take us back 2 billion years in evolution. Thus, cocaine alters a neural circuit in the brain that is of fundamental importance to survival. Such alterations affect the individual in profound ways that scientists are still trying to understand.
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