Academic Biography

Dr. Steven Robert Laviolette is assistant professor in the Department of Anatomy and Cell Biology at the University of Western Ontario, and NARSAD Young Investigator.  His research focus is to discover and characterize the neurobiological processes of nicotine and opiate addiction.  He is particularly interested in what he calls the biological “switch” from the acute (non-addicted) to the dependent (addicted) phase after exposure to nicotine. 

Nicotine Addiction

Nicotine is the highly addictive, stimulating and mood altering active chemical in cigarettes.   Health Canada reports that 6 million Canadians are dependent on nicotine.  Nicotine addiction rates are particularly high – up to 85% - among people diagnosed with schizophrenia.

Project Summary

With this grant, Dr. Laviolette and his team are conducting a study using rats to investigate how the biological, chemical, and electrical activity within a region of the brain known as the ‘reward circuit’ change following different phases of nicotine exposure: acute, dependent, and withdrawal.  To investigate increased vulnerability to nicotine addiction among people diagnosed with schizophrenia, they will also examine the how nicotine exposure affects the ability of the brain to adjust its response to stimulation (sensory gating) on a cellular level.

Biological Background and Rationale

We are motivated to engage in behaviour necessary to our survival – to find food, to reproduce, and to seek shelter – because the stimuli associated with these behaviours are linked with sensations of pleasure by the brain’s reward circuit.  However, the reward circuit is also implicated in motivating drug use and drug dependence: stimuli associated with drug use are also linked with reinforcing sensations of pleasure.   The exact biological and chemical mechanisms that lead to dependence, and the specific neurons within the reward circuit that are altered in this process, are not well understood.   Dr. Laviolette’s aim is to characterize the mechanisms of nicotine action on the reward circuit throughout different phases of exposure to nicotine.

Information about how well the body’s needs are being met is communicated to a group of neurons within the reward circuit by the neuron-to-neuron chemical messenger (neurotransmitter) acetylcholine.  Acetylcholine binds with specialized molecules on the neurons’ surface (nicotinic acetylcholine receptors) to initiate a sequence of events within the neuron that results in the release of another neurotransmitter called dopamine.  Nicotine can imitate the action of acetylcholine by binding to nicotinic acetylcholine receptors.  This activity is independent, and in excess of, of the natural stimulation that these neurons receive.  In either case, the stimulated neurons release neurotransmitter dopamine to neurons in the next region in the reward cycle.

Behaviours that increase dopamine release in the reward circuit generally lead to sensations of pleasure and are reinforced.  But when behaviours that cause abnormally high dopamine release continue, the brain cells of the reward circuit adapt to counteract the effect of this excessive stimulation of the reward circuit rather than continue to reinforce the behaviour to the same degree.  Adaptation causes an overall decrease in the activity of the reward system and feelings of pleasure in response to stimuli.  This effect partially explains the physical aspects of drug tolerance (the need for more of the drug for the desired effect) and dependence and withdrawal (the need of the drug to feel normal and unpleasant symptoms in its absence). 

During the first and second part of this study, Dr. Laviolette will investigate the nature of the neuron-to-neuron connections in the reward circuit throughout different phases of nicotine exposure.  To accomplish this, he will strategically isolate certain receptors by blocking the activity at other receptors with drugs, to find where, in the circuit and in individual neurons, the critical adaptations that cause the ‘switch’ to nicotine addiction occur.

When we are surrounded by many sounds from different sources, we could experience this as senseless and overwhelming noise, but most people automatically separate overlapping noises into meaningful information and ignore the irrelevant sounds.  This process is called auditory sensory gating, and problems with this process are a common symptom of schizophrenia that is linked to auditory hallucinations.  Several lines of investigation also support the link between sensory gating deficits and nicotine abuse.  Furthermore, post-mortem studies of brain structure show that people diagnosed with schizophrenia have below average numbers of nicotinic acetylcholine receptors, and drug studies show that nicotine, which stimulates nicotinic acetylcholine receptors, reduces sensory gating deficits.   

For this reason, Dr. Laviolette proposes that nicotine use might be a form of ‘self-medication,’ making people with sensory gating deficits more vulnerable to nicotine abuse and dependence.  In the final stage of this study, Dr. Laviolette will investigate a possible connection between nicotine use and symptoms of schizophrenia.

Outcome

This research will provide us with detailed information about the biology of nicotine addiction in healthy and schizophrenic populations.  The results of this experiment could also be applied to find more effective treatment methods for nicotine addiction.  Dr. Laviolette suggests that with sufficient information the processes that lead to dependence may be prevented or reversed.  The information gained from the third part of the investigation could lead to healthier methods of treating sensory gating deficits and auditory hallucinations for people diagnosed with schizophrenia.