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Neurobehavioral consequences of adolescent nicotine exposure

Institution: Scripps Research Institute
Investigator(s): Cindy Ehlers, Ph.D.
Award Cycle: 2001 (Cycle 10) Grant #: 10RT-0334 Award: $630,710
Subject Area: Nicotine Dependence
Award Type: Research Project Awards

Initial Award Abstract
Recent health surveys have revealed that over 20% of all adolescents, between the ages of 12 and 18, are smokers. In young adults who decide to smoke, smoking onset appears to peak between the ages of 14-16 years. Unfortunately, beginning smoking during young adulthood has been shown to produce several serious outcomes. Adolescent smokers are more likely to become heavy smokers, they are much less likely to quit smoking later in their life, and are more likely to die from smoking-related illnesses. This suggests the initiation of smoking during adolescence will continue to have dramatic long-term consequences on world-wide health care costs. It has been suggested that these findings of poorer outcome for early onset smokers may due to the fact that young adults may be at higher risk for developing a stronger physical dependence on smoking. Thus it appears that smoking is “more addictive” when a person begins smoking during adolescence. The reason for this higher risk for addiction to smoking during adolescence is not entirely understood. However, it is likely due to the fact that the brain goes through rapid and dramatic physical changes during that time. This developmental process allows the brain to assume its adult form. It appears that this brain process while critical for adult development also puts the brain “at risk” for drug abuse and perhaps also the toxic effects of drugs. It seems that changes that occur in the adolescent brain may resemble in some ways another critical time in development that occurs during late fetal development. We have demonstrated, in animal studies, that nicotine exposure during early life has long term consequences for brain development. However, there have been fewer systematic studies assessing the long-term effects of nicotine on brain and behavior in animals exposed during adolescence. In many ways the development of the rat brain is similar to the development of the human brain with both rat and human brains having similar critical periods of development. Therefore, animal models of nicotine exposure have the potential to allow us to greatly enhance our understanding of nicotine's effects during adolescence. Our studies propose to develop the use of transdermal nicotine patches to expose adolescent rats to relevant doses of nicotine. Brain measures such as electroencephalography (brain waves, EEG) and event-related potentials (ERPs) are very sensitive to changes in central nervous system function which occur as a result of nicotine exposure. These brain measures as well as assessment of critical behaviors will allow us to more fully assess the effects of adolescent nicotine exposure. We predict that chronic nicotine exposure during adolescence alters brain mechanisms involved in the regulation of stress and anxiety. Given that smoking has been related to stress levels, these alterations in response to stress are bound to alter future smoking patterns. Thus the proposed experiments will examine long term changes in brain function and behavior following adolescent nicotine exposure. This will lay the foundation for identifying what brain systems are particularly affected by adolescent nicotine exposure.

Lasting effects of adolescent nicotine exposure on the electroencephalogram, event related potentials, and locomotor activity in the rat.
Periodical: Brain Research. Developmental Brain Research Index Medicus:
Authors: Slawecki CJ, and Ehlers CL ART
Yr: 0 Vol: Nbr: Abs: Pg:

Chronic nicotine or ethanol exposure in adolescent rats: Preliminary behavioral results.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Slawecki CJ, Betancourt M, Li Cole M, and Ehlers CL ABS
Yr: 2000 Vol: 26 Nbr: 1 Abs: 483.12 Pg: 1308

Adolescent nicotine exposure: Long-term effects on neurophysiology and response to CRF in rats.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Slawecki CJ, Betancourt M, Roth J, and Ehlers CL ABS
Yr: 2001 Vol: Nbr: Abs: 667.3 Pg:

Blunted cortical EEG responses to CRF in adult rats exposed to nicotine during adolescence.
Periodical: Neuropeptides Index Medicus:
Authors: Slawecki CJ, Ehlers CL ART
Yr: 2003 Vol: 37 Nbr: 1 Abs: Pg: 66-73

Increased anxiety-like behavior in adult rats exposed to nicotine as adolescents.
Periodical: Pharmacology Biochemistry and Behavior Index Medicus:
Authors: Slawecki Cj, Gilder A, Roth J, Ehlers CL ART
Yr: 2003 Vol: 75 Nbr: Abs: Pg: 355-361

Long term neruophysiological effects of alcohol or nicotine exposure in adolescent animal models.
Periodical: New York Academy of Sciences Index Medicus:
Authors: Slawecki CJ, Ehlers CL ABS
Yr: 2004 Vol: 1021 Nbr: Abs: Pg: 448 - 452