Nicotinic receptors tolerance development

Marks Ml, Collins AC (1982) Characterization of nicotine binding in mouse brain and comparison with the binding of a-bungarotoxin and quinuclidinyl benzilate. Mol Pharmacol 22 554-564 Marks Ml, Burch JB, Collins AC (1983) Effects of chronic nicotine infusion on tolerance development and nicotinic receptors. J Pharmacol Exp Ther 226 817-825 Marks Ml, Stitzel JA, Romm E, Wehner JM, Collins AC (1986) Nicotinic binding sites in rat and mouse brain comparison of acetylchohne, nicotine, and alpha-bungarotoxin. Mol Pharmacol 30 427 36... 

Marks Ml, Campbell SM, Romm E, Collins AC (1991) Genotype influences the development of tolerance to nicotine in the mouse. J Pharmacol Exp Ther 259 392 02 Marks MJ, Pauly JR, Gross SD, Deneris ES, Hermans-Borgmeyer I, Heinemann SF, Collins AC (1992) Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment. J Neurosci 12 2765-2784... 

Marks MJ, Burch JB, CoUins AC (1983) Effects of chronic nicotine infusion on tolerance development and iticotinic receptors. J Pharmacol Exp Ther 226 817-825... 

Repeated exposure, as occurs in habitual smokers, leads to an increased rate of metabolism of nicotine and decreased sensitivity of the receptors to the nicotine. More nicotine is therefore required to satisfy the needed stimulation, and tolerance develops. This is a separate effect from addiction which seems to be due to increased levels of a substance called dopamine in the brain. This is due to the nicotine activating nerve cells which results in increased release of dopamine and causes a reduction in the amount of an enzyme that destroys dopamine. It seems that other addictive drugs may also work by increasing dopamine levels. 

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