Advances in association of genetic polymorphisms within the dopaminergic system with nicotine dependence

Abstract

Nicotine is the main compound in cigarettes which leads to smoking addiction. Nicotine acts on the limbic dopamine reward loop in the midbrain through binding to nicotinic acetylcholine receptors, promoting the release of dopamine, resulting in a rewarding effect or satisfaction. This satisfaction is essential for continued and compulsive tobacco use, and therefore dopamine plays a crucial role in nicotine dependence (ND). Numerous studies have identified genetic polymorphisms of dopaminergic pathways which may influence nicotine susceptibility and the degree of addiction. Dopamine levels are greatly influenced by synthesis, storage, release, degradation, and reuptake related genes, including genes encoding tyrosine hydroxylase (TH), dopamine decarboxylase (DDC), dopamine transporter (DAT1/SLC6A3), dopamine receptor (DRD), dopamine 3-hydroxylase (DBH), catechol oxygen methyltransferase (COMT), and monoamine oxidase (MAO). In this paper, we review research progress on the effects of polymorphisms in the above genes on downstream smoking behavior and ND, to provide a theoretical basis for the elucidation of the genetic mechanism underlying ND and future personalized treatment for smoking cessation.