There are many types of nerve cells in the nervous system and, in general, each type releases one major chemical which conveys information to adjacent nerve cells or tissues. Because they transmit information throughout the nervous system, these chemicals are called neurotransmitters. The cells upon which these neurotransmitters act possess special proteins on their membranes which are able to recognize each unique type of neurotransmitter. These proteins are called receptors. The interaction of neurotransmitters with receptors is the primary mechanism whereby information is passed along to other nerve cells. The intricate network of billions of nerve cells allows the brain to process information in a highly organized and complex manner giving rise to thoughts, memories, emotions, etc.
One of the major neurotransmitters in the nervous system is called acetylcholine. Acetylcholine can interact with two kinds of receptors, muscarinic and nicotinic, named after the plant products which were first shown to produce similar effects (muscarine from mushrooms and nicotine from tobacco respectively). In particular, nicotinic receptors have been among the most thoroughly studies of all neurotransmitter receptors. In the peripheral nervous system, acetylcholine acting on nicotinic receptors is responsible, either directly or indirectly, for almost all muscle and organ activity, both voluntary (such as walking and writing) or involuntary (such as heart beats and digestion).
In the brain, nicotinic receptors have been shown to mediate a number of important functions. Nicotine in tobacco products stimulates nicotinic receptors on many types of nerve cells, and this generally leads to a modest increase in the release of other neurotransmitters in the brain. In particular, nicotine has been shown to stimulate the release of the neurotransmitter, dopamine. An elevation in brain dopamine levels appears to be responsible for the positively reinforcing properties of many drugs as well as behaviors. There are, however, several unique features of nicotine's effects which gives it a distinctive biological profile, especially when exposure is intermittent but long-term, as with cigarette smoking.
One feature of nicotine's effects is that, immediately following exposure to nicotine, there is a loss of activity towards the drug. This phenomenon is known as desensitization. One possible consequence of the desensitization process is that long-term nicotine use appears to cause the body to maintain additional nicotinic receptors upon which the neurotransmitter, acetylcholine, acts in an attempt to counteract the loss of activity. This increased number of receptors is called receptor upregulation. Although nicotinic receptor upregulation has been demonstrated after chronic nicotine administration as well as cigarette smoking, neither the physiological significance nor the relationship with the desensitization process are known.
Research in my laboratory has been investigating the effects of both short-term and chronic nicotine exposure on the ability of the drug to release dopamine from several specialized areas of the brain, the striatum (important in modulating muscle activity), the hippocampus (important in learning and memory function), and the nucleus accumbens (important for pleasure and reward). By carefully controlling drug delivery, time-course, concentrations, administration schedules and recovery periods, and then measuring the resulting effects on brain nicotine levels, brain receptor number and activity, and neurotransmitter release, we have begun to understand how the processes of receptor desensitization and receptor upregulation are related, and to what extent prior exposure to the drug influences the responses to nicotine.
The results obtained from this research have provided important new information in our quest to understand the processes involved in nicotine's effects, and how exposure to the drug from cigarette smoke or nicotine patches and gum influences the central nervous system. For more complete information on our findings, refer to the accompanying list of publications resulting from our work.