Smoking cigarettes is one of the hardest addictions to end, because many regions of the brain are wired for reinforcement of smoking. Nicotine, the main active component of cigarettes, acts on nicotinic acetylcholine receptors in the brain. Nicotine withdrawal symptoms include irritability, sleep problems, inattention, increased appetite and craving for cigarettes.
Ventral Tegmental Area
The ventral tegmental area, or VTA, includes neurons whose cell bodies are in the VTA but have projections and release neurotransmitters into the nucleus accumbens, or NAc. The VTA-NAc dopaminergic pathway, also called the mesolimbic dopamine pathway, is considered the "reward pathway." Nicotinic acetylcholine receptors are found on neurons that release the neurotransmitter dopamine from the VTA into the NAc. Smoking cigarettes increases dopamine release in the NAc, causing reinforcement of smoking. When smokers try to quit, the decrease in dopamine release leads to cigarette cravings and hampers the ability to not relapse.
The VTA also releases dopamine into the frontal cortex, making up the mesocortical dopamine pathway. A small amount of dopamine is also released into the hippocampus and amygdala.
Nucleus Accumbens
The NAc receives dopamine from the VTA. Nicotinic receptors also exist on the post-synaptic side of these dopaminergic neurons, meaning nicotine in the NAc can influence the release of dopamine in the NAc. As the NAc is important for reinforcement of pleasurable behaviors, nicotine withdrawal leads to craving for more cigarettes.
Frontal Cortex
The frontal cortex is a brain region involved in strategy, planning and what is often described as "free will." Dopamine from the VTA is released into the frontal cortex. As nicotinic receptors located on dopamine neurons in the VTA can modulate dopamine release, smoking can increase dopamine release in the frontal cortex. Nicotine withdrawal leads to less dopamine in the frontal cortex, leading to the withdrawal symptoms of poor attention.
Hippocampus
The VTA also releases a small amount of dopamine into the hippocampus. The hippocampus controls learning and memory and is important for context cues that trigger relapse. Nicotine withdrawal leads environments associated with smoking to elicit strong cravings, as the hippocampus has glutamatergic connections to the NAc.
Amygdala
The VTA also releases a small amount of dopamine into the amygdala. The amygdala controls emotional responses and also has a glutamatergic connection to to the NAc. Nicotine withdrawal can produce irritability because less dopamine is released from the VTA to the amygdala. Brain cells that release opioids, known as the body's natural painkillers, into the amygdala also have nicotinic receptors on them. Thus, nicotine withdrawal can reduce opioid release into the amygdala, triggering cravings.
References
- "Molecular Neuropharmacology: A Foundation for Clinical Neuroscience," Eric Nestler, Steven Hyman, and Robert Malenka; 2001
- NIDA: Tobacco Facts
- Psychology; "The Motivational Impact of Nicotine and Its Role in Tobacco Use"; Rick A. Bevins and Anthony R. Caggiula; 2009
