Authors Subjects Method Intervention Results a) Animal Studies         Marenco et al. [156] Rats- chronically nic exposed vs. nic naive 2-deoxy-D-[1-14C] glucose autoradiography SC nic (0.4 mg/kg) vs. saline ↑­ thal, superior colliculus in chronically exposed; ­ thal, superior colliculus, medial habenula and dorsal lateral geniculate in nic naive London et al. [38, 39] Rats 2-deoxy-D-[1-14C]glucose autoradiography SC nic (0.1 to 1.75 mg/kg) ↑­ nicotine rich regions, including thal, cereb, visual system, others b) Human Studies         Staley et al. [86] 16 smokers 16 non-smokers 5 IA-SPECT Recent abstinence ↑­ Striatum, Parietal cortex, frontal cortex, anterior cingulated, temporal cortex, occipital cortex, cerebellum Zubieta et al. [43] 19 smokers 15O-PET Nicotine containing versus denicotinized cigarettes ↓­ global blood flow Stapleton et al. [27] 4 smokers; 2 non-smokers 2 FDG-PETs (Fully quantified) IV nic (1.5 mg) versus placebo ↓global and most regions studied Yamamoto et al. [25] 10 smokers 99mTc-ECD SPECT Cigarette vs. abstinence ↓global blood flow Rose et al. [35] 34 smokers 15O-PET Cigarette vs. no nic control conditions ↑L frontal factor (incl prefrontal and ACC),↓ L amyg rCBF Zubieta et al. [40] 18 smokers 15O-PET Nic nasal spray vs. pepper spray ↑anterior thal; ↓ L ant temp and R amyg Domino et al. [26] 11 smokers FDG-PET Nic nasal spray vs. pepper spray Small ↓ global; ↑ L IFG, L PC, R thal, visual cortex; ↓ normalized L ins and R inf occ ctx Domino et al. [37] 18 smokers 15O-PET Nic nasal spray vs. pepper spray ↑ thal, pons, visual cortex, cereb Stein et al. [36] 16 smokers fMRI IV nic (0.75- 2.25 mg/70 kg wt) vs. placebo ↑ R NAc and bilateral amyg, cingulate, frontal lobes, thal, others Rourke et al. [28] 8 smokers; 8 former smokers; 17 non-smokers iodine-123 iodoamphetamine (IMP) SPECT Smokers smoked the morning of the scan; other groups did not ↓ cortical uptake of IMP (a measure of blood flow) in current smokers compared to other groups All regional changes represent normalized activity, unless otherwise stated. SC = subcutaneous; nic = nicotine; thal = thalamus; cereb = cerebellum; SPECT = single photon emission computed tomography; fMRI = functional magnetic resonance imaging; IV = intravenous; R = right; L = left; NAc = nucleus accumbens; amyg = amygdala; FDG = 18F-fluorodeoxyglucose; PET = positron emission tomography; IFG = inferior frontal gyrus; PC = posterior cingulate; ins = insula; inf occ ctx = inferior occipital cortex; ant = anterior; temp = temporal lobe; ACC = anterior cingulate cortex

Table 1: Functional brain imaging studies of nicotine or cigarette administration.