Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D-2/D-3 dopamine system

摘要

Investigations on the acute effects of alcohol in the human mesolimbic dopamine D-2/D-3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D-2/D-3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D-2/D-3 receptor ligand [F-18] fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D-2/D-3 binding potential. Twenty-four healthy male mu-opioid receptor (OPRM1) 118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BPND) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BPND was observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BPND in extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p= 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p= 0.001)). The acute alcohol effects on the D2/D3 dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D2/D3 receptors may hint at an addiction relevant trait.