You are your brain

Nicotine is an active principle which is found in tobacco leaves. Its popularity is due to the effects this natural alkaloid produces in our brain.

Inside our body it exists different types of receptors that are activated once they bind to acetylcholine. There are two types of receptors: nicotinic receptors, which are also activated by nicotine, and muscarinic receptors, which are activated by muscarine, an alkaloid present in Amanita muscaria.

Nicotinic receptors can be found in the periphery, that is, in the postsynaptic membrane of skeletal muscle fibers, and in the central nervous system. The axon terminals of the neurons secrete acetylcholine, that binds to the postsynaptic membrane receptor. This causes the opening of cation channels, creating the depolarization of that neuron. As a result, peripheral receptors cause a muscle contraction and a nerve impulse is transmitted through depolarization by central receptors.

The amount of nicotine per cigarette (no more than 3 mg) is not enough to activate peripheral receptors of neuromuscular junction since a high concentration is needed, but they can bind to central nervous system receptors and activate or desensitize them (desactivate), depending on the dose.  The effects of nicotine depend on the localization of these receptors.

Let us see the path of nicotine inside our body. The smoke of the cigarette goes inside our lungs, the nicotine reaches the pulmonary alveolus and it is absorbed into the bloodstream through the respiratory membrane. Once the nicotine is in the bloodstream, it substitutes the acetylcholine, acting on two principal neural systems where nicotine has a substantial effect on. These systems are: mesolimbic system and septo-hyppocampal system. 

Mesolimbic system plays a fundamental role in dependence syndrome. Nicotine binds to the receptors of interneuron presynaptic membrane that inhibits the dopamine transmission of ventral tegmental area and desensitize them. This way, the inhibition of neurons which secrete dopamine gets interrupted and it creates an increase in this neurotransmitter. The release of dopamine stimulates the gratification and, therefore, the dependence. The continued exposure to nicotine increases the number of receptors at the level of inhibitory interneurons, creating the necessity of increasing even more the nicotine dose in order to get the initial gratification. The explanation is due to the amount of receptors which remain active is lower, and interneurons respond by increasing the number.

Septo-hyppocampal system is substantial in learning and memory abilities. Nicotine acts also at this level since this system is composed by cholinergic neurons that use the action of nicotinic receptors. All the effects of nicotine are not negative. If it is used in a moderate way, some learning and memory functions can be potentially stimulated, creating beneficial effects in our brain. This means that nicotine is not directly responsible for all the pathologies related to consumption of tobacco, but dependence. Moreover, dependence is the main cause of the immediate effects of tobacco because of the release of catecholamines in the bloodstream, such as the increase of heart rate and blood pressure.

Nicotine must be metabolized and eliminated from our body. The metabolization is carried out by a cytochrome P450 enzyme (CYP2A6). This is a polymorphous enzyme, its effects may vary depending on the person. Some people can metabolize nicotine faster than other. The degree of susceptibility to nicotine dependence will be higher or lower depending on the type of enzyme we have. Nicotine will remain much longer inside the body of a person with a slower metabolism, which means that this person won't need to consume nicotine for longer than someone with a faster metabolism.