Nicotine has high affinity for nicotinic acetylcholine receptors located in both the central nervous system (CNS) and periphery. Binding on the ligand-gated channel opens the cannel, which facilitates the entry of sodium or calcium into the cell. The entry of cations activates voltage-dependent calcium channels which in turn also facilitates calcium entry into the cell. The net result of nicotine acting on cells that control dopamine release is the increase in dopamine in the nucleus accumbens and forebrain areas. Nicotine stimulated dopamine release following a single intraperitoneal nicotine injection will produce an over 200% increase in dopamine in the nucleus accumbens that lasts for over 90 minutes. In addition, other constituents of tobacco smoke can contribute to tobacco addiction. The condensation products of acetaldehyde in cigarette smoke inhibit monoamine oxidase type A and B which would decrease the metabolism of dopamine, norepinephrine and serotonin. The increase in dopamine due its reduced metabolism would also play a role in the biological and behavioral effects of smoking. Thus there is a large body of evidence that the increased dopamine release in the nucleus accumbens and forebrain structures is the major factor producing the rewarding, conditional reinforcement and reinforcement enhancing effects of nicotine.