Subjective and Neural Responses to Intravenous Alcohol in Young Adults with Light and Heavy Drinking Patterns

Abstract

Heavy alcohol consumption during young adulthood is a risk factor for the development of serious alcohol use disorders. Research has shown that individual differences in subjective responses to alcohol may affect individuals' vulnerability to developing alcoholism. Studies comparing the subjective and objective response to alcohol between light and heavy drinkers (HDs), however, have yielded inconsistent results, and neural responses to alcohol in these groups have not been characterized. We performed a double-blind, placebo-controlled, randomized crossover alcohol challenge study comparing functional magnetic resonance imaging and subjective response to intravenously administered 6% v/v ethanol to a target blood alcohol concentration of 0.08% or placebo between HDs and social drinkers (SDs). During the imaging, we presented emotional cues in order to measure how emotion modulated the effects of alcohol on the brain's reward circuitry. We found that, at equivalent blood alcohol concentrations, HDs reported lower subjective alcohol effects than SDs. Alcohol significantly activated the nucleus accumbens in SDs, but not in HDs. Self-reported ratings of intoxication correlated with striatal activation, suggesting that activation may reflect subjective experience of intoxication. Fearful faces significantly activated the amygdala in the SDs only, and this activation was attenuated by alcohol. This study shows that HDs not only experience reduced subjective effects of alcohol, but also demonstrate a blunted response to alcohol in the brain's reward system. Our findings indicate that reduced subjective and neural response to alcohol in HDs may be suggestive of either the development of tolerance to alcohol, or of pre-existing decreased sensitivity to alcohol's effects.

The effect of alcohol priming on neural markers of alcohol cue-reactivity

“…The assessment of alcohol craving using alcohol cue reactivity paradigms offers unique opportunities for translational science, as alcohol craving can be measured in many contexts, such as within behavioral, neural, and clinical frameworks (2). Importantly, fMRI techniques have been coupled with intravenous alcohol administration, enabling the detection of neural responses related to the acutely rewarding effects of alcohol, namely activation of the striatal reward circuitry (3, 4). …”

Dutasteride reduces alcohol’s sedative effects in men in a human laboratory setting and reduces drinking in the natural environment

“…During the 90 days prior to study enrollment, subjects drank on an average of 2.2 days (DD) per week, with 0.7 heavy drinking days (HDD) per week (i.e., >4 standard drinks), and consumed an average of 8.1 sd per week. Because subjective responses to alcohol have been reported to differ in heavy vs. light drinkers (King et al 2002; Gilman et al 2012), we subdivided the sample into nonhazardous or light drinkers (LD), n =37 (<15 sd/week and not more than 1 HDD per month during the past 90 days consistent with safe drinking guidelines) and hazardous or heavy drinkers (HD), n =33, who either drank heavily more than once per month or consumed ≥15 drinks per week. Drinking measures from the 90-day timeline follow-back (TLFB) are shown in Table 1.…”

Variation in AKR1C3, which encodes the neuroactive steroid synthetic enzyme 3α-HSD type 2 (17β-HSD type 5), moderates the subjective effects of alcohol

“…During the 90 days prior to study enrollment, subjects reported an average of 2.3 drinking days (DD) per week, with 0.7 heavy drinking days (HDD) per week (i.e., > 4 standard drinks in a day), consuming an average of 8.1 standard drinks (SD) per week. Because subjective responses to alcohol have been reported to differ in heavier and lighter drinkers (King et al 2002; Gilman et al 2012), we used baseline drinking reports to characterize subjects as non-hazardous or lighter drinkers (LDs), n=34 (<15 SD/week and not more than 1 HDD per month during past 90 days consistent with safe drinking guidelines) and hazardous or heavier drinkers (HDs), n=31, who either drank heavily more than once per month or consumed ≥15 drinks per week. Drinking measures from the 90-day TLFB for the two baseline drinking groups are shown in Table 1.…”

“…We tested whether the moderation by AKR1C3* 2 genotype of subjective effects differed by drinker status based on prior observations that subjective effects of alcohol differ based on drinker status (King et al 2002; Gilman et al 2012). Table 5 presents mixed model results that include AKR1C3*2 genotype and baseline drinker status as factors.…”