Tolerance to nicotine develops with chronic smoking and may be associated with the onset of tobacco dependence. It is unclear how quickly this tolerance dissipates after terminating exposure to nicotine. We propose to longitudinally assess responses to measure doses of nicotine by nasal spray in 30 male and female smokers as they smoke ad lib for two days (baseline), quit for six days, and then resume smoking for two days on the GCRC. We hypothesize that responses to nicotine will become larger over the six days of cessation, showing dissipation of tolerance and then be smaller during the final two days of ad lib smoking, showing reinstatement of tolerance with return to smoking.
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