Nicotinic Research and Therapeutics Program
Our laboratory has had a major focus on understanding the role of central nervous system (CNS) nicotinic cholinergic receptors in normal and abnormal human cognition for over 20 years. Nicotinic receptors are ligand-gated ion channels that occur on the surface of neurons (nerve cells) in the brain and serve to modulate neuronal transmission. Nicotinic receptors bind the naturally occurring neurotransmitter acetylcholine and of course nicotine. Research from this laboratory and others has shown that nicotinic receptors appear to be important in regulating learning and memory, anxiety, and motor performance as well as attention and impulsivity.
Our research has investigated the role of nicotinic receptor functioning in learning and memory both in normal individuals and those with neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease as well as neurodevelopmental disorders like Attention-Deficit/Hyperactivity Disorder.
See below for details on our different studies on nicotine and Aging, ADHD, and Parkinson's Disease.
Nicotine and Healthy Aging
Prior research has shown that the cholinergic system is the primarily responsible for cognitive symptoms in seen in people with dementia. What remains uncertain is the role that the cholinergic system in general and a subset of receptors called the nicotinic system plays in cognition in healthy non-demented older adults (referred to as normal cognitive aging). This is critical because the ever growing healthy aging population will show declines in cognition that fall short of dementia but still impact functional abilities and independence. In dementia structural changes in the nicotinic system appear to be related to cognitive dysfunction. However, in normal aging there is no evidence for structural changes in the nicotinic system but age-related functional differences exist. The preservation of structural aspects of the nicotinic system in normal aging implies that a manipulation to enhance nicotinic functioning may lessen the cognitive symptoms of aging. As the search continues for safe and effective cognitive enhancers, it will be important to understand the role of the nicotinic system in cognitive aging and whether nicotinic mechanisms have the potential to benefit cognition in healthy adults.
The Nicotinic Cholinergic System and Cognitive Aging Research Study
We are seeking healthy 21-30 year olds and 65-75 year olds for a neuroimaging study. We will examine the role of a chemical system in the healthy aging brain and its role in memory and thinking processes. You may be eligible if you are between 21-30 years old or 65-75 years old, are healthy, non-smoking, and are not currently taking any medications for psychiatric disorders. The study involves a screening visit (about 3 hours) followed by 3 study visits (about 6 hours each). Study visit days include IV placement, fMRI scans, cognitive tasks and blood draws. Participants may receive up to $400 in compensation.
For more information, please call 802-847-8248 or email firstname.lastname@example.org
Nicotine and ADHD
Adolescents who suffer from Attention-Deficit/Hyperactivity Disorder (ADHD) become cigarette smokers and tobacco users at twice the rate of non-ADHD adolescents. While ADHD first appears in childhood the symptoms persist into adolescence and adulthood for up to 80% of people who are diagnosed as children. Similarly, the high rate of tobacco use continues into adulthood. The reasons for this vulnerability of people with ADHD to tobacco are poorly understood.
One possible reason is that nicotine, the psychoactive component of tobacco, may produce positive effects on attentional performance in ADHD adolescents. ADHD produces specific attentional difficulties which are partially ameliorated by medications that enhance dopaminergic functioning in the brain. Extensive studies of nicotine over several decades from our laboratory and others have demonstrated that nicotine has significant attentional and cognitive-enhancing effects even in clinical populations with neuropsychiatric disorders. It is therefore possible that tobacco use in adolescents serves as a form of self-selected medication to improve some of the cognitive difficulties associated with ADHD.
We are examining whether nicotine, the psychoactive constituent of tobacco, may have positive effects on cognitive and motor processes involving attention that appear to be impaired in many adolescents and young adults with ADHD. The primary aim of these studies is to examine the effects of acute nicotinic stimulation on a measure of behavioral inhibition, decision-making, and motor performance in adolescents and adults with ADHD. These results should provide significant information as to some of the reasons for the vulnerability of the ADHD population to high rates of tobacco use, and may help in the future development of better and safer alternative treatments for ADHD.
The Effects of Nicotine and Ritalin on the ADHD Brain: The goal of this study is to use functional MRI to examine how nicotine improves impulse control and working memory in young adults (18-25) who either have or do not have ADHD. This study will look at patterns of brain activation associated with nicotine and methylphenidate (Ritalin, a common treatment for ADHD) to help understand how the differences in the brain functioning of people who have ADHD may affect their behavior. We are looking for 24 non-smoking young adults (18-25) who have, and 24 who do not have, ADHD. The volunteers will complete three 6-hour study visits in which they will receive nicotine alone, methylphenidate alone, or placebo and then be asked to perform computer tasks in the fMRI.
Nicotine and Parkinson's Disease
Principal Investigator: James Boyd, M.D.
In recent years, a group of behavior changes collectively called impulse control disorders have been identified in Parkinson's disease (PD). Acetylcholine is a chemical in the brain which works to regulate the effects of dopamine. It has been known for many years that nicotine imitates many of the actions of acetylcholine. In preliminary studies, nicotine has been shown to reduce impulsive behavior in Attention Deficit Hyperactivity Disorder. By administering nicotine across the skin using a patch, we hope to better understand whether nicotine may act to improve impulse control disorders in PD without needing to reduce or stop PD medications.
Nicotine Treatment of Impulsivity in Parkinson's Disease: The study will examine whether treatment with nicotine (delivered through the skin via a patch) improves computer-based laboratory and clinical measures of impulsive and compulsive behaviors in those with Parkinson's disease who have recently experienced an impulse control disorder (ICD).