Dopamine D2 Receptor Availability is Associated with Subjective Responses to Alcohol

Abstract

Resting D2 receptor availability may predict healthy subject responses to alcohol exposure.

High Levels of Dopamine D2 Receptors in Unaffected Members of Alcoholic Families

“…Also, a recent study documented that subjects with high D 2 receptor availability showed higher levels of intoxication after alcohol than subjects with low D 2 receptor levels, who showed blunted responses. 16 Inasmuch as subjects with blunted responses to alcohol have been shown to have a higher risk of alcoholism, 3 the latter study is also consistent with the hypothesis that high D 2 receptor availability may be protective. Moreover, preclinical studies have shown that in rodents trained to selfadminister alcohol, D 2 receptor overexpression in nucleus accumbens markedly reduces alcohol intake both in rats that are genetically predisposed to self-administer alcohol (alcohol-preferring rats) 24 and in those that are not (Sprague-Dawley) 25 ; this finding provides evidence that high D 2 receptor availability may interfere with alcohol intake, even in animals that are genetically prone to administering alcohol.…”

“…15 In humans, imaging studies have shown that differences in D 2 receptor availability in nonalcoholic subjects are associated with differences in sensitivity to the intoxicating effects of alcohol. 16 Levels of D 2 receptor may also be involved with alcohol addiction, as evidenced by imaging and postmortem studies showing reductions in D 2 receptor levels in the striatum from the brains of alcoholic subjects. [17][18][19][20] Because low D 2 receptor availability in striatum has also been documented in other drug addictions when compared with non-drug-abusing control subjects, it has been postulated that this reduction may render an individual more vulnerable to substance abuse.…”

Intravenous Ethanol Increases Dopamine Release in the Ventral Striatum in Humans: PET Study Using Bolus-Plus-Infusion Administration of [11C]raclopride

“…3 The second study showed that oral alcohol induced a Ethanol increases striatal dopamine release S Aalto et al decrease in [ 11 C]raclopride binding in the VST, which is consistent with increased DA release, but the effect varied considerably among the subjects. 4 The lack of positive findings in two studies using intravenous ethanol intervention might have been caused by methodological limitations, e.g., a fixed order of repeated PET scans, differences in intervention timing, 5 or insufficient sensitivity. 6 In the next study, the same group showed that intravenous ethanol administration with neutral (non-alcohol-related) cues induced a 12% decrease in BP ND in the left NAcc, suggesting ethanol-induced increase in DA concentration.…”

“…4 Two studies using prolonged stable intravenous ethanol infusion during PET data acquisition failed to detect changes in striatal [ 11 C]raclopride binding. 5,6 However, in another study, the same group reported that intravenous ethanol without alcohol-related cues increased, but alcohol-related cues alone (without ethanol intervention) decreased DA concentration in the limbic striatum. 7 A recent study applying oral alcohol administration, found a systematic decrease in [ 11 C]raclopride binding in all striatal subregions, suggesting a quite non-specific DA release in male subjects.…”

The anxious amygdala: CREB signaling and predisposition to anxiety and alcoholism

“…Psychostimulants, opioids, and alcohol all increase synaptic DA accumulation within this important brain region (5). With PET imaging, we and others (6)(7)(8) have shown that mesolimbic DA release following drug administration is correlated with positive subjective effects. Preclinical studies have shown that drug reward can be attenuated by pharmacological or genetic manipulations that alter mesolimbic DA neurotransmission (9).…”