Nucleus accumbens serotonin transporters in alcoholics measured by whole-hemisphere autoradiography.
Nucleus accumbens (NAC) is regulated by the dopaminergic and serotonergic pathways, and it is a brain area with a crucial role in the rewarding effects of ethanol. In this preliminary study, possible alterations of [3H]citalopram binding to serotonin transporter (SERT) were evaluated in the NAC of Cloninger type 1 and 2 alcoholics (nine and seven subjects, respectively), and nonalcoholic controls (10 subjects) by human postmortem whole-hemisphere autoradiography. The [3H]citalopram binding in the NAC was 35% higher in the alcoholics than in the controls; in the type 1 alcoholics, the binding was 54% and in the type 2 alcoholics it was 17% higher. Although the effect size showed medium effects (0.49-0.60), the results did not reach statistical significance due to large standard deviations. The [3H]citalopram binding declined significantly with age in the controls, but not in the alcoholics. In the controls, there was a significant positive correlation between the [3H]citalopram binding in the NAC and in the anterior cingulate gyrus, an area in which the [3H]citalopram binding has been shown to be lower among alcoholics. On the contrary, a significant negative correlation was observed in the type 2 alcoholics and no correlation in the type 1 alcoholics. In addition, there was a strong tendency toward a positive correlation between the SERT and dopamine transporter binding in the type 2 alcoholics, but not in the other groups. These preliminary results suggest a differential monoaminergic imbalance in type 1 and 2 alcoholism in brain areas important for the regulation of motivation, reward, and reinforcement.
Storvik
Markus
M
Department of Pharmacology and Toxicology, University of Kuopio, FI-70210, Finland. markus.storvik@uku.fi
Tiihonen
Jari
J
Haukijärvi
Tuija
T
Tupala
Erkki
E
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000378:metabolism*; D001345:Autoradiography / Q000379:methods; D001665:Binding Sites; D016022:Case-Control Studies; D015283:Citalopram / Q000378:metabolism; D005260:Female; D005387:Finland; D006801:Humans; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism; D014316:Tritium
D015283:Citalopram; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014316:Tritium; C493230:SLC6A4 protein, human