Is Nicotine a ‘Gateway Drug’ for Cocaine?

Is Nicotine a ‘Gateway Drug’ for Cocaine?Despite the differences in their legal status, both nicotine and cocaine are known for their ability to cause physical dependence and addiction. The path to dependence and addiction typically begins when use of a given substance makes changes in the way the brain produces or breaks down dopamine, a naturally occurring chemical that plays several key roles inside the brain and body. Current evidence indicates that nicotine and cocaine alter the brain’s dopamine levels in highly similar ways. In addition, the ongoing presence of nicotine makes the brain more susceptible to cocaine’s effects and prepares the ground for cocaine addiction.

The Basics

Dopamine functions as a neurotransmitter inside the brain and spinal cord. This means that it passes between nerve cells called neurons and relays specific chemical messages that change how those neurons behave and communicate with each other. Dopamine is only found in certain areas of the brain, but its effects are widespread. In a group of neurons known collectively as the ventral tegmental area (VTA), it helps control processes related to learning and memory, human motivation and susceptibility to drug addiction. Dopamine that originates in the VTA travels to a nearby group of brain structures known collectively as the limbic system. Inside this system, it activates the neurons required for the production of pleasurable sensations inside the body. Virtually every substance with a potential to trigger physical dependence and addiction achieves its basic effects by artificially hiking levels of dopamine inside the brain. Some substances hike dopamine levels by directly increasing dopamine output in certain neurons; others hike dopamine levels by blocking the recycling process that normally breaks the chemical down into its constituent parts. In addition, some substances drastically increase dopamine levels by simultaneously engaging in both of these activities. While the primary addiction-related effects of heightened dopamine levels occur in the limbic system, significant effects also occur within the ventral tegmental area. In order to produce changes within the brain’s neurons, dopamine and all other neurotransmitting chemicals attach themselves to specific sites on the neurons’ surfaces known as receptors. However, not all receptors respond to the same neurotransmitters; instead, any given type of neurotransmitter must have specific physical or chemical characteristics that allow it to gain access to any given type of receptor. This means that there are specific receptors for dopamine, as well as for other neurotransmitting chemicals such as serotonin and norepinephrine. Nicotine, cocaine, and other addictive substances alter the levels of dopamine and other neurotransmitters by either blocking normal activity at neuron receptor sites or mimicking neurotransmitters and plugging into those receptor sites.

Smoking’s Effects

According to a study published in 2011 in the Journal of Neuroscience, a single cigarette releases enough nicotine into the body to change normal function in the VTA and trigger dopamine increases that last for several days. Over time, repeated smoking leads to two important changes in this brain region. First, perpetually increased dopamine levels produce the sorts of pleasurable sensations that start a smoker down the path to addiction. In addition, the presence of nicotine alters memory and learning within the VTA and encourages a pattern of learned behavior that supports smoking in the future. Critically, the authors of the study also found that nicotine achieves part of its effects in the VTA by chemically activating the same dopamine receptors that get activated by cocaine.

Impact on Cocaine Addiction

Most cocaine abusers and addicts are smokers whose nicotine use began before the first use of cocaine. At one time, doctors and researchers considered this fact to be nothing more than a statistical coincidence. However, according to the results of a multi-university study published in 2011 in the journal Science Translational Medicine, the long-term presence of nicotine in the brain actually intensifies the brain’s response to cocaine, and also makes it more likely that cocaine users who smoke will eventually become cocaine addicts. This process works on two levels. First, the presence of nicotine makes a specific gene, called the FosB gene, more active than usual; in turn, when activated, the FosB gene makes the brain more susceptible to cocaine’s addictive properties. In addition, the presence of nicotine alters the function of the dopamine-sensitive neurons in the brain that extend from the VTA up through the limbic system. In turn, these alterations reinforce the pleasurable responses, learning patterns and behavioral patterns that support the onset of cocaine addiction. While smoking increases the risks for cocaine abuse and addiction, cocaine abuse and addiction do not increase the risks for smoking, the authors of the study in Science Translational Medicine report.

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