Neurobiology of Nicotine and Non-nicotine Components of Tobacco Addiction
Status:
Completed
Trial end date:
2011-11-01
Target enrollment:
Participant gender:
Summary
In the present study the investigators will measure the effects of nicotine and non-nicotine
factors on brain function during cognitive processes that are differentially sensitive to
these factors. One process-continuous working memory (CWM)-is implemented via a network of
frontal and parietal brain regions and is highly dopamine dependent. Smoking cessation
results in significant deficits in CWM which can persist for weeks and are reversed by
resumption of nicotine administration in the form of smoking or nicotine replacement.
Additionally, CWM deficits are observed during smoking of denic cigarettes. Brain function
during CWM is modulated by smoking abstinence and subsequent nicotine administration and
activity in the dlPFC is implicated in these effects. Collectively, these data suggest that
CWM is highly sensitive to the nicotine, but not non-nicotine components of smoking. Brain
function during CWM is altered by smoking abstinence and nicotine, but the effect of smoking,
in the absence of nicotine, has not been evaluated.
Another process-cue-reactivity (CR)-results from the repeated pairing of otherwise neutral
stimuli with nicotine administration. Acute smoking cessation has not been shown to have
strong effects on CR in the form of cue-provoked craving, nor has nicotine replacement been
shown to have robust effects on CR. Likewise, the direct effects of smoking abstinence on
brain CR have been small; though craving has been shown to modulate relations between
abstinence and CR. Moreover, recent data from our lab suggest larger 'doses' of abstinence (~
24 hrs) may amplify brain responses to cues. The effect of smoking in the absence of
nicotine, on CR has not, to our knowledge, been evaluated. Collectively, these data suggest
that CR in the form of cue-induced craving is not highly sensitive to the effects of
short-term smoking abstinence or nicotine. Brain CR is modulated by abstinence-induced
craving and longer-term abstinence, but it is unclear whether abstinence from nicotine or
non-nicotine components is responsible for these effects.
In the present study, we propose to evaluate the effects of non-nicotine and nicotine factors
on CWM and CR using functional magnetic resonance imaging. This method allows for the
non-invasive assessment of brain function. We will also examine the role of genes in
moderating and mediating the effects of nicotine and non-nicotine factors on cognitive
function