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Nicotine causes dose-dependent release of DA in the striatum

1 cigarette contains ~1mg nicotine which results in a ~ 0.014mg/kg dose to a 70kg human. Nicotine causes dose-dependent release of DA in the striatum. 0.025mg/kg. 0.050mg/kg. Dose-dependent IV nicotine-induced DA release in the rat nucleus accumbens (Pontiere et al, 1996). 1.

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Nicotine causes dose-dependent release of DA in the striatum

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  1. 1 cigarette contains ~1mg nicotine which results in a ~0.014mg/kg dose to a 70kg human. Nicotine causes dose-dependent release of DA in the striatum 0.025mg/kg 0.050mg/kg Dose-dependent IV nicotine-induced DA release in the rat nucleus accumbens (Pontiere et al, 1996) 1

  2. Doses of amphetamine that produced a 600% increase in DA only caused ~20% decrease in BPND(Seneca et al, 2006). DA release measured via PET is a saturating signal Simulations suggest that at least a 200% increase in DA is necessary for a 5-10% decrease in [11C]raclopride BPND. 2

  3. Previous nicotine-induced DA studies with PET • Mixed results from previous [11C]raclopride studies of nicotine-induced DA release. • Motion artifact?

  4. Each subject will receive 2 scans on separate days (rest and smoking conditions). Vicra optical tracking system to measure subject motion during scan at 20Hz. Reconstruct dynamic scan data with information from the Vicra. Subjects will smoke 1 or more cigarettes during the scan. Ventilation and filter system to capture smoke. Proposed study design motion recorded during 2 SUCCESSIVE cigarettes 4

  5. view from behind scanner real time view on monitor motion recorded during smoking 3 cigarettes motion recorded during “baseline”

  6. Subjects/Eligibility • Men and women, aged 18-45 years • DSM-IV criteria for nicotine dependence via structured clinical interview diagnostic (SCID) • Fagerstrom Test for Nicotine Dependence (FTND) rating of at least 3 • Using > 10 cigarettes per day for at least 1 year • CO levels > 10 ppm during intake evaluation • no exclusion for drinking alcohol 6

  7. Proposed analysis • Estimate DBPND by Logan plot or SRTM. • Apply “ntPET” analysis to estimate time-varying DA signal ( • Investigate relationship between outcome measures (BPND and FDA) and behavioral data (FTND, years smoked, craving, nicotine high, etc). 7

  8. Preliminary Results • To date 6 subjects have successfully been scanned: 4 B, 2 B/I Rest Smoking 8

  9. ΔBPND was calculated as and agrees with previous reports. Significant correlations were found between ΔBPND in the left dorsal caudate and FTND and between ΔBPND in the right ventral striatum and number of years of smoking n=5, p < 0.05 n=5, p < 0.05 VERY PRELIMINARY RESULTS n = 6 ΔBPND FTND ΔBPND years of smoking

  10. Preliminary temporal analysis Model without dopamine change Model with Dopamine change Model-predicted dopamine response to smoking two cigarettes starting at 45 min. Note: this is the response at a SINGLE voxel in the dorsal caudate.

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