Corticostriatal and Dopaminergic Response to Beer Flavor with Both fMRI and [(11) C]raclopride Positron Emission Tomography

Abstract

Background: Cue-evoked drug-seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine (DA) transmission. Using [(11) C]raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST DA release in beer drinkers, inferred by RAC displacement. Here, a subset of subjects from this previous RAC-PET study underwent a similar paradigm during functional magnetic resonance imaging (fMRI) to test how orbitofrontal cortex (OFC) and VST blood oxygenation level-dependent (BOLD) responses to beer flavor are related to VST DA release and motivation to drink.

Methods: Male beer drinkers (n = 28, age = 24 ± 2, drinks/wk = 16 ± 10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and Gatorade(®) (appetitive control). We tested for correlations between BOLD activation in fMRI and VST DA responses in PET, and drinking-related variables.

Results: Compared to Gatorade, beer flavor increased wanting and desire to drink, and induced BOLD responses in bilateral OFC and right VST. Wanting and desire to drink correlated with both right VST and medial OFC BOLD activation to beer flavor. Like the BOLD findings, beer flavor (relative to Gatorade) again induced right VST DA release in this fMRI subject subset, but there was no correlation between DA release and the magnitude of BOLD responses in frontal regions of interest.

Conclusions: Both imaging modalities showed a right-lateralized VST response (BOLD and DA release) to a drug-paired conditioned stimulus, whereas fMRI BOLD responses in the VST and medial OFC also reflected wanting and desire to drink. The data suggest the possibility that responses to drug-paired cues may be rightward biased in the VST (at least in right-handed males) and that VST and OFC responses in this gustatory paradigm reflect stimulus wanting.

Keywords: Alcohol; Cue Reactivity; Ethanol; Nucleus Accumbens; Orbitofrontal Cortex.

Figure 1. fMRI: Paradigm

Following a water baseline, six scans alternated beer or Gatorade flavor administration, with water interspersed within-scan. Subjective ratings followed the water baseline and each scan, indicated by vertical arrows (↑). Scan length=4:48, w=3 water sprays, B=4 preferred beer sprays, G=4 Gatorade sprays. Spray vol. ~0.75 ml each; flavor order counterbalanced between subjects (beer first shown here).

Figure 2. fMRI: Subjective ratings

Subjects (n=28) rated perceptions of flavor stimuli and wanting/desire for beer. (A) Beer and Gatorade were perceived as equally intense; note that the y-axis mirrors the rating scale. (B) Beer flavor was less pleasant than Gatorade, but similar to water. (C) Beer flavor increased wanting for beer and desire to drink. Baseline (water) was rated before scanning; beer and Gatorade ratings shown here are means of three ratings collapsed across scans of the same tastant. VAS = visual analog scale, #p<0.05 compared to water, *p<0.05 compared to Gatorade.

Figure 3. Response to beer flavor compared to appetitive control

Voxelwise t-statistic map illustrating (A) right VST and (B) orbitofrontal cortex (OFC) BOLD response to alcohol flavor CS in n=28 male drinkers. Search regions are outlined in green. Effects illustrated at a voxel-wise display threshold, p<0.01, uncorrected; k=100.

Figure 4. Correlations between wanting and [beer flavor > Gatorade] BOLD contrast

Voxelwise t-statistic map shows significant positive correlation with “number of beers wanted” in (A) right VST and (B) medial OFC (search regions in green). Effect illustrated at a display threshold, p<0.01, uncorrected; k=100.

Figure 5. PET

Right VST DA response to beer flavor compared to Gatorade [ΔBP_ND > 0] in (n=28) male drinkers, display height threshold p<0.01, uncorrected, k=5.