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Fraser Trevor Fraser Trevor Author
Title: Several lines of research suggest that dysfunction of central dopaminergic and serotonergic neurotransmission predisposes to alcohol dependence and contributes to the maintenance of excessive alcohol consumption
Author: Fraser Trevor
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Mesolimbic dopaminergic and serotonergic pathways. (Photo credit: Wikipedia ) Several lines of research suggest that dysfunction of c...
Mesolimbic dopaminergic and serotonergic pathways.
Mesolimbic dopaminergic and serotonergic pathways. (Photo credit: Wikipedia)
Several lines of research suggest that dysfunction of central dopaminergic and serotonergic neurotransmission predisposes to alcohol dependence and contributes to the maintenance of excessive alcohol consumption R1315511BABBHGHJR1315511BABCDJFH. In rodents, ethanol-induced dopamine release in the mesolimbic reward system reinforces alcohol intakeR1315511BABBEIHDR1315511BABCHHFB. Reduced homovanillic acid concentrations in cerebrospinal fluid (CSF) and a relatively increased density of dopamine uptake sites in the basal ganglia have been observed in alcohol-naive vervet monkeys that later developed alcohol preference R1315511BABCFFGG. It has been hypothesized that alcohol releases dopamine in the ventral striatum by reversing dopamine uptake, so that dopamine transporters begin to release intra­cellular dopamine R1315511BABBCJDI. Chronic alcohol consumption, on the other hand, has been associated with an increased dopamine turnover rate and decreased dopamine uptake sites and sensitivity of postsynaptic dopamine receptorsR1315511BABCFFGGR1315511BABDIDBJR1315511BABBCDBH.
Another series of studies suggest that ethanol-induced reward may be independent of the activation of dopamine D2 receptors and may be mediated through serotonin 5-HT1B and 5-HT2 receptorsR1315511BABDIIHIR1315511BABDIHGH. Increased sensitivity of postsynaptic serotonin receptors may be due to reduced serotonin turnover, which in rodents and nonhuman primates has been associated with impaired impulse control and increased alcohol consumptionR1315511BABCDJFHR1315511BABCFFGGR1315511BABDEDIC. In humans, low 5-hydroxyindoleacetic acid in CSF has been associated with aggressive behavior and early-onset alcoholismR1315511BABDDDBJR1315511BABCDHAC. A facilitatory role for reduced functional capacity of serotonin transporters in rodents has been suggested as a pathogenic factor in alcohol dependenceR1315511BABBGHGC. Therefore, we examined dopamine and serotonin uptake sites in recently abstinent alcohol-dependent patients and healthy volunteers with the use of single photon emission computed tomography (SPECT) and the radioligand [123I]╬▓-CIT, which shows specific displacement by pharmaceuticals that bind to dopamine transporters in the basal ganglia and to serotonin uptake sites in the brainstem R1315511BABBADIJR1315511BABCEJGB. In the brainstem, the highest density of serotonin transporters is found in the raphe nuclei R1315511BABDADEC.
We assessed 1) the association between dopamine and serotonin uptake sites and chronic alcohol consumption and 2) the impact of these factors on behavioral measures that have previously been associated with them (e.g., impulsivity, anhedonia, depression, and anxiety). Moreover, we controlled for the effects of smoking on monoamine uptake sites, because over 80% of chronic alcoholics smoke, and nicotine may alter central dopamine release and metabolism R1315511BABBFGFBR1315511BABBBGFI.
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