Etiology and Pathophysiology - Nicotine Dependence

Etiology and Pathophysiology

Nicotine dependence has been called a “pediatric disease” since most smokers started during adolescence. By the age of 18, 90% of those who will ever try a cigarette have done so, and age 18 years is the average age at which individuals become daily smokers. As with other substance use disorders, the etiology of nicotine dependence is multifactorial and includes biological, psychological and social factors, including genetic factors.

Nicotine is the primary psychoactive agent in tobacco smoke and smokeless tobacco and has powerful addictive proper-ties. As an indication of the addictive potential of this substance, one-third to one half of all children and adolescents who smoke one cigarette progress to become habitual users. Nicotine is con-sidered to be the “gateway drug” to the use of other substances.

Nicotine has a multitude of effects. Some are acute, while others appear only after chronic usage. It acts in two primary ar-eas of the brain: the mesolimbic dopaminergic system (the brain reward pathway), which is related to the euphoriant effects of the drug, and the locus coeruleus, which mediates stress reac-tions and vigilance and relates to the higher mental and cognitive functions. There are specific nicotine receptor sites (the nicotinic cholinergic receptors) throughout the central nervous system in the hypothalamus, hippocampus, thalamus, midbrain, brain stem and cerebral cortex. In addition, nicotine affects nearly all as-pects of the endocrine–neuroendocrine system, including the catecholamine, serotonin, corticosteroid and pituitary hormones. Its endocrine effects are mediated via the hypothalamic–pitui-tary axis and the adrenal medullary cortex. Centrally it causes release of acetylcholine, norepinephrine, serotonin, dopamine, vasopressin, growth hormone, corticotropin, cortisol, prolactin and endorphins.

Nicotine has stimulant and depressive effects on both the central and the peripheral nervous systems. It also affects the cardiovascular system, the gastrointestinal system and the skel-etal motor system. Nicotine stimulates the cholinergic nervous system (sympathetic and parasympathetic). Through this variety of central and peripheral actions, nicotine improves mood and decreases anxiety; decreases distress in response to stressful stimuli and decreases aggression; improves overall cognitive function and performance (improves reaction time, concentra-tion, vigilance and stimulus-processing capacity, increases at-tention, memory and learning, improves the ability to disregard irrelevant stimuli); and decreases the appetite for simple carbo-hydrates, decreases stress-induced eating and increases resting metabolic rate. Many individuals soon become tolerant to these effects so that they smoke not to achieve them, but rather to avoid withdrawal symptoms.