This video explains the pathophysiologic changes behind nicotine addiction, it identifies nicotinic acetylcholine receptor as  a key protein for the development of dependence.

Transcript of the video narration:

“Although nicotine can interact with a variety of receptor at numerous tissues, it is its interaction with specific receptors in the brain that creates the dependence associated with smoking.

Within the midbrain, nicotine interacts with the alpha 4 beta 2 nicotinic acetylcholine receptor. Acetylcholine is the natural ligand for this receptors. However, nicotine also an acetylcholine receptor agonist, has a higher affinity for the α4β2 (alpha 4 beta 2) receptors. Located on postsynaptic neurons, these receptors are comprised by two α4 and three β2 subunits that form a channel for transporting ions through the membrane.

When two molecules of nicotine or another ligand engage binding sites within the ionotropic receptor, the ion channel is activated. Looking into the receptor, we see that it is closed, but activation by ligand triggers channel opening for the passage of calcium, sodium and potassium ions.This generates action potentials to the reward area of the brain. Here, the impulse stimulates the release of neurotransmitters including dopamine. Dopamine triggers additional signaling events that stimulate the reward circuit generating short feelings of well-being, increased attention and improved mood. Every time tobacco is used, dopamine levels surge. However, nicotine is eliminated rather rapidly, causing dopamine levels to decline. The result: a craving for more nicotine.

With continued use, α4β2 (alpha 4 beta 2) nicotinic receptors undergo complex adaptive changes including up regulation and desensitization. Over time, these and other downstream changes contribute to a stronger need for nicotine stimulation to achieve the rewards of smoking.”

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