In a patient who has smoked for many years, what mechanism explains the pleasurable sensation from nicotine leading to addiction?

The pleasurable sensation from nicotine leading to addiction is primarily due to increased release of dopamine in the nucleus accumbens. When nicotine is inhaled, it rapidly crosses the blood-brain barrier and stimulates nicotinic acetylcholine receptors in the brain. This stimulation leads to the release of dopamine, a neurotransmitter that plays a crucial role in the brain's reward circuitry.

The nucleus accumbens is a major component of the mesolimbic dopamine pathway, which is essential for the sensation of pleasure and reinforcement. When dopamine is released in this area, it creates feelings of euphoria and reinforces the behavior of seeking out nicotine, contributing to its addictive potential. This is why nicotine is considered highly addictive; it creates a cycle where the drug reinforces the behavior leading to repeated use, as the brain starts to associate nicotine intake with pleasurable feelings.

Other mechanisms mentioned do not directly account for the primary addictive qualities of nicotine.