How does cocaine produce its effects?

A great amount of research has been devoted to understanding the way cocaine produces its pleasurable effects, and the reasons it is so addictive. One mechanism is through its effects on structures deep in the brain. Scientists have discovered regions within the brain that, when stimulated, produce feelings of pleasure. One neural system that appears to be most affected by cocaine originates in a region, located deep within the brain, called the ventral tegmental area (VTA). Nerve cells originating in the VTA extend to the region of the brain known as the nucleus accumbens, one of the brain's key pleasure centers. In studies using animals, for example, all types of pleasurable stimuli, such as food, water, sex, and many drugs of abuse, cause increased activity in the nucleus accumbens.

Cocaine in the brain - In the normal communication process, dopamine is released by a neuron into the synapse, where it can bind with dopamine receptors on neighboring neurons. Normally dopamine is then recycled back into the transmitting neuron by a specialized protein called the dopamine transporter. If cocaine is present, it attaches to the dopamine transporter and blocks the normal recycling process, resulting in a build-up of dopamine in the synapse which contributes to the pleasurable effects of cocaine.

Researchers have discovered that, when a pleasurable event is occurring, it is accompanied by a large increase in the amounts of dopamine released in the nucleus accumbens by neurons originating in the VTA. In the normal communication process, dopamine is released by a neuron into the synapse (the small gap between two neurons), where it binds with specialized proteins (called dopamine receptors) on the neighboring neuron, thereby sending a signal to that neuron. Drugs of abuse are able to interfere with this normal communication process. For example, scientists have discovered that cocaine blocks the removal of dopamine from the synapse, resulting in an accumulation of dopamine. This buildup of dopamine causes continuous stimulation of receiving neurons, probably resulting in the euphoria commonly reported by cocaine abusers.

As cocaine abuse continues, tolerance often develops. This means that higher doses and more frequent use of cocaine are required for the brain to register the same level of pleasure experienced during initial use. Recent studies have shown that, during periods of abstinence from cocaine use, the memory of the euphoria associated with cocaine use, or mere exposure to cues associated with drug use, can trigger tremendous craving and relapse to drug use, even after long periods of abstinence.

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