Nicotinic modulation of dopamine release during development
Abstracts
Initial Award Abstract |
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More and more teenagers are using and becoming addicted to cigarettes everyday. Of the adult smokers today, 4 out of 5 claim to have started the habit before age 18. Among the teenage cigarette users, a larger number of females smoke than males. With the growing rate of pregnancies among teenage girls, the issue of the consequences of smoking on the developing child is becoming a topic of concern. Smoking during pregnancy is already known to cause adverse effects in the child later in life, such as hyperactivity and learning disorders. Nicotine is the compound in tobacco that is responsible for the addictive properties of cigarettes and is also believed to be responsible for some of the adverse effects of smoking on the child. Within the brain, nicotine acts on proteins known as nicotinic acetylcholine receptors. These receptors are widely distributed within the brain, are there even before birth, and are located on numerous neurotransmitter systems. Nicotine, acting on its receptors, causes release of these neurotransmitters, one of which is dopamine. Nicotine induced dopamine release is what causes people to become addicted to cigarettes. Changes in the development of the dopamine system of the child as a result of exposure to nicotine prematurely (e.g. in the womb) is thought to be the cause of some of the negative outcomes of cigarette use during pregnancy. The purpose of the proposed study is to use a rat model to first determine if any differences exist in the nicotinic acetylcholine receptors located on the dopamine brain cells of the pre-adolescent (before puberty) vs. the adult rat. Second, the ability of nicotine to regulate the release of dopamine will be evaluated in the preadolescent and adult brains to determine if the regulation of dopamine release by nicotine is similar in the younger vs. the older animals. The ability of nicotine to regulate the release of dopamine will be studied separately in male and female rats to determine if sex differences exist in the actions of nicotine. Finally, pregnant rats will be treated with nicotine throughout pregnancy and the changes in the nicotine's ability to regulate the release of dopamine will be examined in the pups. The results should provide information about whether there are age and/or sex differences in the nicotine's regulation of dopamine release in the younger brain, which may underlie the early start of cigarette use by teenagers and the higher prevalence of smoking among females. Answers may also be revealed about some of the underlying causes of the negative effects of nicotine exposure during pregnancy. |
Final Report |
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More and more teenagers are using and becoming addicted to cigarettes everyday. Of the adult smokers today, 4 out of 5 claim to have started the habit before age 18. Among the teenage cigarette users, there are a large number of female smokers, and with the growing rate of pregnancies among teenage girls, the issue of the consequences of smoking on the developing child is becoming a topic of concern. Smoking during pregnancy is already known to cause adverse effects in the child later in life, such as hyperactivity and learning disorders. Nicotine is the compound in tobacco that is responsible for the addictive properties of cigarettes and is also believed to be responsible for some of the adverse effects of smoking on the child. Within the brain, nicotine acts on proteins known as nicotinic receptors. These receptors are widely distributed within the brain and they are there even before birth. Nicotine, acting on its receptors, causes the release of dopamine. Nicotine-induced dopamine release is what causes people to become addicted to cigarettes. Changes in the development of the dopamine system of the child as a result of exposure to nicotine prematurely (e.g. in the womb) is thought to be the cause of some of the negative outcomes of cigarette use during pregnancy. However, the crucial time-points during which the dopamine system is susceptible to nicotine exposure are as yet unknown. The purpose of the proposed study is to use an animal model to first determine when nicotinic receptors first appear on the dopamine neurons. Second, determine if any differences exist in the nicotinic receptors located on the dopamine brain cells during development. Third, the ability of nicotine to regulate the release of dopamine will be compared in younger vs. older animals. Nicotine-stimulated dopamine release will be studied to examine sex differences in the actions of nicotine. The results indicate that functional nicotinic receptors are present very early within the developing dopamine neurons of both males and females. This finding indicates that nicotine can act directly on immature dopamine neurons and alter their development. The results also show that nicotine can release more dopamine from the reward pathway of the adolescent animals, indicating that nicotine may in fact be more addictive in the young. We are currently testing this hypothesis in animal models of nicotine reinforcement. This study, along with my own in vitro data, will provide an understanding of the underlying causes of high prevalence of smoking among juveniles. |
