Nicotine and Cocaine Act Similarly on the Brain’s Reward System

Posted on May 5th, 2011

New research has found that the effects of nicotine on the brain are similar to the effects of cocaine. This could help explain why some people find it so difficult to quit smoking. Being exposed to nicotine for 15 minutes caused a long-term increase in the excitability of neurons that are involved in the reward system of the brain; the same system that is involved in cocaine use. This suggests that the nicotine and cocaine affect similar mechanisms of memory to create long-lasting changes in the brain.

Danyan Mao, PhD, postdoctoral researcher at the University of Chicago Medical Center, said that everything starts from the first exposure—whether it’s nicotine or cocaine—and that the researchers wanted to discover what happens in the brain when a person is first exposed to a cigarette that might lead to a second cigarette.

Previous research has found that nicotine can promote plasticity (the long-term strengthening and weakening of the connections between neurons in the brain) in a brain region called the ventral tegmental area (VTA). Neurons that originate in this region release the transmitter dopamine, which plays an important role in the effects of addictive drugs and natural stimulants like food and sex.

Daniel McGehee, PhD, a neuroscientist and associate professor in the Department of Anesthesia & Critical Care at the University of Chicago Medical Center who has studied nicotine and plasticity, said that a single exposure to nicotine can lead to changes in the synapses of the brain that can last for several days; this finding is important in understanding how people become addicted to nicotine and other substances.

In the current study, Mao and colleagues monitored the electrical activity of VTA dopamine neurons in slices of brain taken from adult rats. Each slice was soaked for 15 minutes in a concentration of nicotine similar to the amount that would reach the brain after smoking one cigarette. After three to five hours, the researchers conducted experiments to detect the presence of synaptic plasticity and to determine which neurotransmitter receptors were involved in its development.

The researchers found that nicotine-induced synaptic plasticity in the VTA is dependent upon a receptor for the neurotransmitter acetylcholine, which is located on the dopamine neurons. They also found that the D5 dopamine receptor, which has previously been associated with the effects of cocaine on the brain, was necessary for the synaptic plasticity. By blocking either of these receptors during nicotine exposure, the drug was unable to alter plasticity.

Mao said that the study found that nicotine and cocaine use similar mechanisms to induce synaptic plasticity in dopamine neurons in the VTA region, and that while the effects of nicotine and cocaine are very different in humans, the overlapping effects of the two substances on the brain’s reward system may explain why both substances are highly addictive.

McGehee added that the notion that nicotine works on the same circuitry as cocaine could point to why some people find it so difficult to quit smoking or using cocaine, and why so many people who experiment with nicotine or cocaine end up developing an addiction.

The effects at the D5 receptor could also help scientists develop new ways to prevent and treat addiction. Current blockers of the receptor also block the D1 receptor, however, which is important for health motivation and movement.

McGehee said that the D5 receptor is a potential target, but scientists need to find a way to tweak the addictive effect of substances like nicotine or cocaine without altering the person’s desire to pursue other healthy, rewarding behaviors.

Source: University of Chicago Medical Center, Nicotine and cocaine leave similar mark on brain after first contact. ScienceDaily, May 4, 2011

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