Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system

Addict Biol. 2017 Sep;22(5):1449-1458. doi: 10.1111/adb.12424. Epub 2016 Jul 11.

Abstract

Investigations on the acute effects of alcohol in the human mesolimbic dopamine D2 /D3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D2 /D3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D2 /D3 receptor ligand [18 F]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 D2 /D3 binding potential. Twenty-four healthy male μ-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.

Keywords: PET; alcohol; dopamine.

MeSH terms

  • Adult
  • Benzamides
  • Central Nervous System Depressants / pharmacology*
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dopamine D2 Receptor Antagonists
  • Ethanol / pharmacology*
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / drug effects*
  • Healthy Volunteers
  • Humans
  • Male
  • Positron-Emission Tomography
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / drug effects*
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / drug effects*
  • Receptors, Dopamine D3 / metabolism
  • Receptors, Opioid, mu / genetics
  • Young Adult

Substances

  • Benzamides
  • Central Nervous System Depressants
  • DRD2 protein, human
  • DRD3 protein, human
  • Dopamine D2 Receptor Antagonists
  • OPRM1 protein, human
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Receptors, Opioid, mu
  • Ethanol
  • fallypride