@article{GleichSpittaButleretal.2020, author = {Gleich, Tobias and Spitta, Gianna and Butler, Oisin and Zacharias, Kristin and Aydin, Semiha and Sebold, Miriam Hannah and Garbusow, Maria and Rapp, Michael Armin and Schubert, Florian and Buchert, Ralph and Heinz, Andreas and Gallinat, J{\"u}rgen}, title = {Dopamine D2/3 receptor availability in alcohol use disorder and individuals at high risk}, series = {Addiction Biology}, volume = {26}, journal = {Addiction Biology}, number = {2}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1369-1600}, doi = {10.1111/adb.12915}, pages = {1 -- 10}, year = {2020}, abstract = {Alcohol use disorder (AUD) is the most common substance use disorder worldwide. Although dopamine-related findings were often observed in AUD, associated neurobiological mechanisms are still poorly understood. Therefore, in the present study, we investigate D2/3 receptor availability in healthy participants, participants at high risk (HR) to develop addiction (not diagnosed with AUD), and AUD patients in a detoxified stage, applying F-18-fallypride positron emission tomography (F-18-PET). Specifically, D2/3 receptor availability was investigated in (1) 19 low-risk (LR) controls, (2) 19 HR participants, and (3) 20 AUD patients after alcohol detoxification. Quality and severity of addiction were assessed with clinical questionnaires and (neuro)psychological tests. PET data were corrected for age of participants and smoking status. In the dorsal striatum, we observed significant reductions of D2/3 receptor availability in AUD patients compared with LR participants. Further, receptor availability in HR participants was observed to be intermediate between LR and AUD groups (linearly decreasing). Still, in direct comparison, no group difference was observed between LR and HR groups or between HR and AUD groups. Further, the score of the Alcohol Dependence Scale (ADS) was inversely correlated with D2/3 receptor availability in the combined sample. Thus, in line with a dimensional approach, striatal D2/3 receptor availability showed a linear decrease from LR participants to HR participants to AUD patients, which was paralleled by clinical measures. Our study shows that a core neurobiological feature in AUD seems to be detectable in an early, subclinical state, allowing more individualized alcohol prevention programs in the future.}, language = {en} } @article{DesernoBeckHuysetal.2015, author = {Deserno, Lorenz and Beck, Anne and Huys, Quentin J. M. and Lorenz, Robert C. and Buchert, Ralph and Buchholz, Hans-Georg and Plotkin, Michail and Kumakara, Yoshitaka and Cumming, Paul and Heinze, Hans-Jochen and Grace, Anthony A. and Rapp, Michael Armin and Schlagenhauf, Florian and Heinz, Andreas}, title = {Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in the ventral striatum}, series = {European journal of neuroscience}, volume = {41}, journal = {European journal of neuroscience}, number = {4}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0953-816X}, doi = {10.1111/ejn.12802}, pages = {477 -- 486}, year = {2015}, abstract = {Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N=27). All participants also underwent 6-[F-18]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation by RPEs nor striatal dopamine synthesis capacity differed between groups. However, ventral striatal coding of RPEs correlated inversely with craving in patients. Furthermore, we found a negative correlation between ventral striatal coding of RPEs and dopamine synthesis capacity in healthy controls, but not in alcohol-dependent patients. Moderator analyses showed that the magnitude of the association between dopamine synthesis capacity and RPE coding depended on the amount of chronic, habitual alcohol intake. Despite the relatively small sample size, a power analysis supports the reported results. Using a multimodal imaging approach, this study suggests that dopaminergic modulation of neural learning signals is disrupted in alcohol dependence in proportion to long-term alcohol intake of patients. Alcohol intake may perpetuate itself by interfering with dopaminergic modulation of neural learning signals in the ventral striatum, thus increasing craving for habitual drug intake.}, language = {en} } @misc{TroppmannBalfanzKrachetal.2014, author = {Troppmann, Britta and Balfanz, Sabine and Krach, Christian and Baumann, Arnd and Blenau, Wolfgang}, title = {Characterization of an Invertebrate-Type Dopamine Receptor of the American Cockroach, Periplaneta americana}, series = {International journal of molecular sciences}, volume = {15}, journal = {International journal of molecular sciences}, number = {1}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms15010629}, pages = {629 -- 653}, year = {2014}, abstract = {We have isolated a cDNA coding for a putative invertebrate-type dopamine receptor (Peadop2) from P. americana brain by using a PCR-based strategy. The mRNA is present in samples from brain and salivary glands. We analyzed the distribution of the PeaDOP2 receptor protein with specific affinity-purified polyclonal antibodies. On Western blots, PeaDOP2 was detected in protein samples from brain, subesophageal ganglion, thoracic ganglia, and salivary glands. In immunocytochemical experiments, we detected PeaDOP2 in neurons with their somata being located at the anterior edge of the medulla bilaterally innervating the optic lobes and projecting to the ventro-lateral protocerebrum. In order to determine the functional and pharmacological properties of the cloned receptor, we generated a cell line constitutively expressing PeaDOP2. Activation of PeaDOP2-expressing cells with dopamine induced an increase in intracellular cAMP. In contrast, a C-terminally truncated splice variant of this receptor did not exhibit any functional property by itself. The molecular and pharmacological characterization of the first dopamine receptor from P. americana provides the basis for forthcoming studies focusing on the significance of the dopaminergic system in cockroach behavior and physiology.}, language = {en} }