Smoking is the leading cause of preventable death in the United States and worldwide.1 In the 20th century, smoking caused 100 million deaths. If present patterns persist, about 1 billion people will die from smoking-related diseases in this century. Finding efficacious treatments for nicotine dependence is an important health goal.2
Nicotine replacement therapy (NRT) is the mainstay of smoking cessation treatment. It includes chewing gum, skin patches, tablets, nasal spray, and inhalers and is designed to decrease withdrawal symptoms by replacing nicotine in the blood. All forms of NRT increase the likelihood that individuals will succeed in their smoking cessation attempts. The various types of NRT are equally efficacious, and additional counseling does not improve an individual's likelihood of success.3
Neuronal pathways involved with nicotine reinforcement. Cholinergic inputs from the caudal part of the pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDTg) stimulate ventral tegmental area (VTA) neurons. The VTA dopamine neuron projection to the nucleus accumbens (nACC) and cortex, the critical substrate for nicotine reinforcement, is modulated by a variety of inhibitory (γ-aminobutyric acid [GABA] and opioid) and excitatory (nicotinic [NIC-R], glutamate [GLU], and cannabinoid-1 receptor [CB1-R]) inputs. The GLU pathways include those that express α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate, and N-methyl-D-aspartate (NMDA) receptors. Serotonin-3 receptors (5-HT3-R) also modulate dopamine release in the nucleus accumbens. Adapted and embellished by Bankole A. Johnson, DSc, MD, PhD, from an original drawing by Dennis Twombly, PhD, at the National Institute on Alcohol Abuse and Alcoholism.
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