Decreased Prefrontal Cortical Dopamine Transmission in Alcoholism

Abstract

Objective Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such working memory, attention, inhibitory control and risk/reward decisions--all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies in alcoholics that have demonstrated less dopamine in the striatum, we hypothesized decreased dopamine transmission in the prefrontal cortex in alcoholism. To test this hypothesis, we used amphetamine and [11C]FLB 457 positron emission tomography (PET) to measure cortical dopamine transmission in a group of 21 recently abstinent alcoholics and matched healthy controls. Methods [11C]FLB 457 binding potential (BPND) was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg−1 of d-amphetamine. Results Amphetamine-induced displacement of [11C]FLB 457 binding potential (Δ BPND) was significantly smaller in the cortical regions in alcoholics compared to healthy controls. Cortical regions that demonstrated lower dopamine transmission in alcoholics included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex and medial temporal lobe. Conclusions The results of this study for the first time unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

Differences in IV alcohol-induced dopamine release in the ventral striatum of social drinkers and nontreatment-seeking alcoholics

“…Given that the VST codes for stimulus valence (Bischoff-Grethe et al, 2009; Mattfeld et al, 2011; Seymour et al, 2007), an attractive interpretation is that IV alcohol intoxication has higher reinforcement value in NTS than in SD. Second, several studies have found that abstinent/detoxified alcoholics have lower psychostimulant-induced increases in DA compared to healthy controls (Martinez et al, 2005; Narendran et al, 2014; Volkow et al, 2007), which is typically taken as evidence for a hypofunctional DA system in chronic alcoholism. However, this phenomenon may be unique to stimulants such as methylphenidate and amphetamine, which have direct and powerful effects on dopamine concentration at the levels of the nerve terminal and synapse.…”

“…Although evidence suggests that alcoholics have functional alteration of the DA system (Martinez et al, 2005; Narendran et al, 2014; Volkow et al, 2007), no research has used an alcohol challenge to induce DA release in dependent drinkers. Prior work examined abstinent alcoholics during treatment and/or withdrawal, and utilized psychostimulants to probe DA function.…”

Heightened Dopaminergic Response to Amphetamine at the D3 Dopamine Receptor in Methamphetamine Users

“…This finding is rather surprising in light of the 'generally accepted' 'blunted theory' of addictionwhich includes the finding of smaller DA release not only in the striatum but also in the extrastriatal regions (Narendran et al, 2014) of stimulants (Martinez et al, 2011;Narendran and Martinez, 2008;Schrantee et al, 2015;Trifilieff and Martinez, 2014;Wang et al, 2012) as well as opiate and alcohol users (Trifilieff and Martinez, 2014). However, it is in line with some (but see Richtand, 2006) preclinical findings suggesting that intermittent repeated exposure to stimulants is associated with a greater dopaminergic response to drugs (ie: sensitization) (Robinson and Berridge, 2001) and that heightened D 3 receptor may be critically involved (Guillin et al, 2001).…”

Dopamine and Alcohol Dependence: From Bench to Clinic

“…A recent PET study [118] demonstrated for the first time that, in addition to the ventral striatum, the long-term consumption of alcohol leads to lowered dopamine levels also in prefrontal cortical structures. These findings support the extensive clinical findings demonstrating that alcohol-dependent individuals have significant impairments in executive functions such as working memory, impulsivity and decision-making; functions governed by the cortical brain structures.…”