Melatonin has been implicated in attenuating an organism's response to drugs of abuse, like cocaine and nicotine. We used melatonin receptor knockout mice to characterize the role of melatonin receptors in regulating nicotine response over the 24-h circadian cycle.
Normal C3H mice have greater nicotine-induced hypothermia and locomotor depression in the light phase than in the dark phase of the circadian cycle. Melatonin 1a knockouts and their wild-type littermates had attenuated response to nicotine, but no significant variation between the light and dark phases. Melatonin 1a knockouts and the wild-types self-administer significantly less nicotine.
Melatonin 1a1b knockouts have increased sensitivity to nicotine, no consistent variation between the light and dark phases, and increased voluntary oral nicotine consumption. Males in the mutant genotypes had increased sensitivity to nicotine compared to females. We conclude that melatonin receptors modulate the physiological response to nicotine, especially in the dark phase of the circadian cycle.
|Commitee:||Ehringer, Marissa, Wright, Kenneth|
|School:||University of Colorado at Boulder|
|School Location:||United States -- Colorado|
|Source:||MAI 46/06M, Masters Abstracts International|
|Subjects:||Neurology, Genetics, Anatomy & physiology|
|Keywords:||Addiction, Circadian rhythms, Melatonin receptor, Nicotine|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be