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  • 1.
    Carvalho, Andre F.
    et al.
    Ctr Addict and Mental Hlth, Canada; Univ Toronto, Canada.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Perez, Augusto
    Corp Nuevos Rumbos, Colombia.
    Probst, Charlotte
    Ctr Addict and Mental Hlth, Canada.
    Rehm, Jurgen
    Ctr Addict and Mental Hlth, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Ctr Addict and Mental Hlth, Canada; Tech Univ Dresden, Germany; Tech Univ Dresden, Germany; Sechenov First Moscow State Med Univ, Russia.
    Alcohol use disorders2019In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 394, no 10200, p. 781-792Article, review/survey (Refereed)
    Abstract [en]

    Alcohol use disorders consist of disorders characterised by compulsive heavy alcohol use and loss of control over alcohol intake. Alcohol use disorders are some of the most prevalent mental disorders globally, especially in high-income and upper-middle-income countries; and are associated with high mortality and burden of disease, mainly due to medical consequences, such as liver cirrhosis or injury. Despite their high prevalence, alcohol use disorders are undertreated partly because of the high stigma associated with them, but also because of insufficient systematic screening in primary health care, although effective and cost-effective psychosocial and pharmacological interventions do exist. Primary health care should be responsible for most treatment, with routine screening for alcohol use, and the provision of a staggered treatment response, from brief advice to pharmacological treatment. Clinical interventions for these disorders should be embedded in a supportive environment, which can be bolstered by the creation of alcohol control policies aimed at reducing the overall level of consumption.

  • 2.
    Filipcic, Igor
    et al.
    Psychiat Hosp Sveti Ivan, Croatia; Josip Juraj Strossmayer Univ Osijek, Croatia; Univ Zagreb, Croatia.
    Filipcic, Ivona Simunovic
    Univ Hosp Ctr Zagreb, Croatia.
    Milovac, Zeljko
    Psychiat Hosp Sveti Ivan, Croatia.
    Sucic, Strahimir
    Psychiat Hosp Sveti Ivan, Croatia.
    Gajsak, Tomislav
    Psychiat Hosp Sveti Ivan, Croatia.
    Ivezic, Ena
    Psychiat Hosp Sveti Ivan, Croatia; Josip Juraj Strossmayer Univ Osijek, Croatia.
    Basic, Silvio
    Josip Juraj Strossmayer Univ Osijek, Croatia; Dubrava Univ Hosp, Croatia.
    Bajic, Zarko
    Psychiat Hosp Sveti Ivan, Croatia.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Efficacy of repetitive transcranial magnetic stimulation using a figure-8-coil or an H1-Coil in treatment of major depressive disorder; A randomized clinical trial2019In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 114, p. 113-119Article in journal (Refereed)
    Abstract [en]

    Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment option for major depressive disorder (MDD). However, comparisons of efficacy between the two FDA-approved protocols of rTMS modalities are lacking. The aim of this industry-independent, randomized-controlled, single-blind trial was to evaluate clinical outcome of the two FDA-approved rTMS protocols delivered by H1-coil and the figure-8-coil, in MDD patients. A total of 228 MDD patients were randomized to 20 sessions of H1-coil or 8-coil as an adjunct to standard-of-care pharmacotherapy, or standard-of-care pharmacotherapy alone. Baseline MDD symptom severity was almost the same in the three groups. Hamilton depression rating scale (HAM-D17) mean score was 17 (5.3) in H1-coil, 17 (5.4) in 8-coil, and 19 (6.1) in control group. The primary outcome was the proportion of patients achieving remission defined as HAM-D17 score amp;lt;= 7 at end-of-treatment at week-4. In the intention-to-treat analysis odds ratio for remission was 1.74 (CI95% 0.79-3.83) in H1-coil compared to the 8-coil group. The difference between two rTMS protocols was not significant. Remission rate was significantly greater in both HF-rTMS groups compared to the control: 60% (CI95% 48-71%), 43% (C195% 31-55%) and 11% (CI95% 5-20%) respectively. The response was significantly better in H1-coil, than in 8-coil group OR = 2.33; CI95% 1.04-5.21 (P = 0.040). The HAM-D17 was lowered by 59% in the H1-coil, 41% in the 8-coil (P = 0.048), and 17% in the control group (P amp;lt; 0.001 vs H1-coil; P = 0.003 vs 8-coil). Safety, tolerability, and the changes in quality of life were comparable. We confirmed the safety and efficacy of both FDA-approved protocols as adjunctive treatments of MDD. Better response rate and greater reduction of depression severity were observed in the H1-coil group, but without a significant difference in the remission rate between the two rTMS modalities.

  • 3.
    Johnstone, Andrea L.
    et al.
    Univ Miami, FL 33136 USA; Univ Miami, FL 33136 USA; EpiCypher Inc, NC USA.
    Andrade, Nadja S.
    Univ Miami, FL 33136 USA.
    Barbier, Estelle
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Khomtchouk, Bohdan B.
    Univ Miami, FL 33136 USA; Univ Chicago, IL 60637 USA.
    Rienas, Christopher A.
    Univ Miami, FL 33136 USA.
    Lowe, Kenneth
    Univ Miami, FL 33136 USA.
    Van Booven, Derek J.
    Univ Miami, FL 33136 USA.
    Domi, Esi
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Esanov, Rustam
    Univ Miami, FL 33136 USA.
    Vilca, Samara
    Univ Miami, FL 33136 USA.
    Tapocik, Jenica D.
    NIAAA, MD USA.
    Rodriguez, Keli
    EpiCypher Inc, NC USA.
    Maryanski, Danielle
    EpiCypher Inc, NC USA.
    Keogh, Michael Christopher
    EpiCypher Inc, NC USA.
    Meinhardt, Marcus W.
    Heidelberg Univ, Germany.
    Sommer, Wolfgang H.
    Heidelberg Univ, Germany.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Zeier, Zane
    Univ Miami, FL 33136 USA.
    Wahlestedt, Claes
    Univ Miami, FL 33136 USA.
    Dysregulation of the histone demethylase KDM6B in alcohol dependence is associated with epigenetic regulation of inflammatory signaling pathways2019In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, article id UNSP e12816Article in journal (Refereed)
    Abstract [en]

    Epigenetic enzymes oversee long-term changes in gene expression by integrating genetic and environmental cues. While there are hundreds of enzymes that control histone and DNA modifications, their potential roles in substance abuse and alcohol dependence remain underexplored. A few recent studies have suggested that epigenetic processes could underlie transcriptomic and behavioral hallmarks of alcohol addiction. In the present study, we sought to identify epigenetic enzymes in the brain that are dysregulated during protracted abstinence as a consequence of chronic and intermittent alcohol exposure. Through quantitative mRNA expression analysis of over 100 epigenetic enzymes, we identified 11 that are significantly altered in alcohol-dependent rats compared with controls. Follow-up studies of one of these enzymes, the histone demethylase KDM6B, showed that this enzyme exhibits region-specific dysregulation in the prefrontal cortex and nucleus accumbens of alcohol-dependent rats. KDM6B was also upregulated in the human alcoholic brain. Upregulation of KDM6B protein in alcohol-dependent rats was accompanied by a decrease of trimethylation levels at histone H3, lysine 27 (H3K27me3), consistent with the known demethylase specificity of KDM6B. Subsequent epigenetic (chromatin immunoprecipitation [ChIP]-sequencing) analysis showed that alcohol-induced changes in H3K27me3 were significantly enriched at genes in the IL-6 signaling pathway, consistent with the well-characterized role of KDM6B in modulation of inflammatory responses. Knockdown of KDM6B in cultured microglial cells diminished IL-6 induction in response to an inflammatory stimulus. Our findings implicate a novel KDM6B-mediated epigenetic signaling pathway integrated with inflammatory signaling pathways that are known to underlie the development of alcohol addiction.

  • 4.
    Jonsson, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Fredlund, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Priebe, Gisela
    Lund Univ, Sweden.
    Wadsby, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Online sexual abuse of adolescents by a perpetrator met online: a cross-sectional study2019In: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 13, no 1, article id 32Article in journal (Refereed)
    Abstract [en]

    Background

    The current study aimed at exploring adolescents’ experiences of online sexual contacts leading to online sexual abuse by a perpetrator whom the victim had first met online. Associations with socio demographic background, experience of abuse, relation to parents, health and risk behaviors were studied.

    Methods

    The participants were a representative national sample of 5175 students in the third year of the Swedish high school Swedish (M age = 17.97). Analyses included bivariate statistics and stepwise multiple logistic regression models.

    Results

    In total 330 (5.8%) adolescents had gotten to know someone during the preceding 12 months for the purpose of engaging in some kind of sexual activity online. Thirty-two (9.7%) of those, the index group, had felt that they had been persuaded, pressed or coerced on at least one occasion. Sexual interaction under pressure was seen as constituting sexual abuse. These adolescent victims of online sexual abuse, the index group, did not differ with respect to socio-demographic background from the adolescents without this experience, the reference group. The index group had significantly more prior experiences of different kind of abuse, indicating that they belong to a polyvictimized group. More frequent risk behavior, poorer psychological health, poorer relationships with parents and lower self-esteem also characterized the index group. Online sexual abuse, without experiences of offline abuse, was associated with a poorer psychological health, at least at the same level as offline sexual abuse only.

    Conclusions

    The study made clear the importance of viewing online sexual abuse as a serious form of sexual abuse. Professionals meeting these children need to focus not only on their psychological health such as symptoms of trauma and depression but also need to screen them for online behavior, online abuse and other forms of previous abuse.

  • 5.
    Mayo, Leah
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    In the face of stress: Interpreting individual differences in stress-induced facial expressions2019In: NEUROBIOLOGY OF STRESS, ISSN 2352-2895, Vol. 10, article id 100166Article, review/survey (Refereed)
    Abstract [en]

    Stress is an inevitable part of life that can profoundly impact social and emotional functioning, contributing to the development of psychiatric disease. One key component of emotion and social processing is facial expressions, which humans can readily detect and react to even without conscious awareness. Facial expressions have been the focus of philosophic and scientific interest for centuries. Historically, facial expressions have been relegated to peripheral indices of fixed emotion states. More recently, affective neuroscience has undergone a conceptual revolution, resulting in novel interpretations of these muscle movements. Here, we review the role of facial expressions according to the leading affective neuroscience theories, including constructed emotion and social-motivation accounts. We specifically highlight recent data (Mayo et al, 2018) demonstrating the way in which stress shapes facial expressions and how this is influenced by individual factors. In particular, we focus on the consequence of genetic variation within the endocannabinoid system, a neuromodulatory system implicated in stress and emotion, and its impact on stress-induced facial muscle activity. In a re-analysis of this dataset, we highlight how gender may also influence these processes, conceptualized as variation in the "fight-or-flight" or "tend-and-befriend" behavioral responses to stress. We speculate on how these interpretations may contribute to a broader understanding of facial expressions, discuss the potential use of facial expressions as a trans-diagnostic marker of psychiatric disease, and suggest future work necessary to resolve outstanding questions.

  • 6.
    Nelson, Britta S.
    et al.
    Univ Georgia, GA 30602 USA.
    Fulenwider, Hannah D.
    Univ Georgia, GA 30602 USA.
    Nennig, Sadie E.
    Univ Georgia, GA 30602 USA.
    Smith, Britessia M.
    Univ Georgia, GA 30602 USA.
    Sequeira, Michelle K.
    Univ Georgia, GA 30602 USA.
    Chimberoff, Scott H.
    Univ Georgia, GA 30602 USA.
    Richie, Christopher T.
    NIDA, MD 20892 USA.
    Cheng, Kejun
    NIAAA, MD USA; NIDA, MD 20892 USA; US FDA, MD USA.
    Rice, Kenner C.
    NIAAA, MD USA; NIDA, MD 20892 USA.
    Harvey, Brandon K.
    NIDA, MD 20892 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Schank, Jesse R.
    Univ Georgia, GA 30602 USA.
    Escalated Alcohol Self-Administration and Sensitivity to Yohimbine-lnduced Reinstatement in Alcohol Preferring Rats: Potential Role of Neurokinin-1 Receptors in the Amygdala2019In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 413, p. 77-85Article in journal (Refereed)
    Abstract [en]

    Genetic factors significantly contribute to the risk for developing alcoholism. To study these factors and other associated phenotypes, rodent lines have been developed using selective breeding for high alcohol preference. One of these models, the alcohol preferring (P) rat, has been used in hundreds of preclinical studies over the last few decades. However, very few studies have examined relapse-like behavior in this rat strain. In this study, we used operant self-administration and yohimbine-induced reinstatement models to examine relapse-like behavior in P rats. Our previous work has demonstrated that P rats show increased expression of the neurokinin-1 receptor (NK1R) in the central nucleus of the amygdala (CeA), and this functionally contributes to escalated alcohol consumption in this strain. We hypothesized that P rats would show increased sensitivity to yohimbine-induced reinstatement that is also mediated by NK1R in the CeA. Using Fos staining, site-specific infusion of NK1R antagonist, and viral vector overexpression, we examined the influence of NK1R on the sensitivity to yohimbine-induced reinstatement of alcohol seeking. We found that P rats displayed increased sensitivity to yohimbine-induced reinstatement as well as increased neuronal activation in the CeA after yohimbine injection compared to the control Wistar strain. Intra-CeA infusion of NK1R antagonist attenuates yohimbine-induced reinstatement in P rats. Conversely, upregulation of NK1R within the CeA of Wistar rats increases alcohol consumption and sensitivity to yohimbine-induced reinstatement. These findings suggest that NK1R upregulation in the CeA contributes to multiple alcohol-related phenotypes in the P rat, including alcohol consumption and sensitivity to relapse. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

  • 7.
    Persson, Emil
    et al.
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Asutay, Erkin
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Löfberg, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Pedersen, Nancy
    Karolinska Inst, Sweden.
    Västfjäll, Daniel
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Decis Res, OR USA.
    Tinghög, Gustav
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Variation in the mu-Opioid Receptor Gene (OPRM1) Does Not Moderate Social-Rejection Sensitivity in Humans2019In: Psychological Science, ISSN 0956-7976, E-ISSN 1467-9280, Vol. 30, no 7, p. 1050-1062Article in journal (Refereed)
    Abstract [en]

    Given previous findings from animal studies and small-scale studies in humans, variation in the mu-opioid receptor gene (OPRM1) has been proposed as a strong biological candidate for moderating sensitivity to social rejection. Using a substantially larger sample (N = 490) than previous studies, a prospective genotyping strategy, and preregistered analysis plans, we tested the hypotheses that OPRM1 variation measured by the functional A118G polymorphism (rs1799971) moderates (a) dispositional sensitivity to rejection and feelings of distress following social exclusion and (b) decision making involving social cognition. In three experimental tasks commonly used to assess altruism, reciprocity, and trust in humans, we found no evidence in favor of the hypotheses; nine main tests were preregistered, and all of them yielded small and statistically insignificant estimates. In secondary analyses, we used Bayesian inference and estimation to quantify support for our findings. Taken together, our results strongly suggest that the link between OPRM1 A118G variation and social-rejection sensitivity is weaker than previously thought.

  • 8.
    Popiolek, K.
    et al.
    Orebro Univ, Sweden.
    Beierot, S.
    Orebro Univ, Sweden.
    Brus, O.
    Orebro Univ, Sweden.
    Hammer, A.
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Leaden, M.
    Gothenburg Univ, Sweden; Karolinska Inst, Sweden.
    Lundberg, J.
    Karolinska Inst, Sweden; Stockholm Cty Council, Sweden.
    Nordanskog, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Nordenskjold, A.
    Orebro Univ, Sweden.
    Electroconvulsive therapy in bipolar depression - effectiveness and prognostic factors2019In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 140, no 3, p. 196-204Article in journal (Refereed)
    Abstract [en]

    Objective Electroconvulsive therapy (ECT) is used in patients with severe forms of bipolar depression. ECT is effective but not all patients respond. The aim of this study was to determine prognostic factors for response to ECT in patients hospitalized for bipolar depression. Methods Data were obtained from several national Swedish registers. All patients with bipolar depression treated with ECT in any hospital in Sweden between 2011 and 2016 for whom information about ECT response was available were included (n = 1251). Response was defined as a score on the Clinical Global Impression - Improvement scale of one or two. Univariate and multivariate logistic regression were conducted to investigate associations between socio-demographic and clinical factors and response. Results Response was achieved in 80.2% patients. Older age was associated with higher response rate to ECT. Patients with comorbid obsessive-compulsive disorder or personality disorder, and patients previously treated with lamotrigine had lower response rate. Conclusion Electroconvulsive therapy for bipolar depression was associated with very high response rates. The strongest prognostic factors were higher age, absence of comorbid obsessive-compulsive disorder or personality disorder, and less prior pharmacologic treatment.

  • 9.
    Rehm, Juergen
    et al.
    CAMH, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Tech Univ Dresden, Germany; IM Sechenov First Moscow State Med Univ, Russia.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Gual, Antoni
    Hosp Clin Barcelona, Spain; IDIBAPS Inst Recerca Biomed Agusti Pi and Sunyer, Spain; Inst Carlos III, Spain.
    ICD-11 for Alcohol Use Disorders: Not a Convincing Answer to the Challenges2019In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277Article in journal (Refereed)
    Abstract [en]

    n/a

  • 10.
    Spagnolo, Primavera A.
    et al.
    NINDS, MD 20892 USA.
    Kimes, Alane
    NIDA, MD 20892 USA.
    Schwandt, Melanie L.
    NIAAA, MD 20892 USA.
    Shokri-Kojori, Ehsan
    NIAAA, MD 20892 USA.
    Thada, Shantalaxmi
    NIDA, MD 20892 USA.
    Phillips, Karran A.
    NIDA, MD 20892 USA.
    Diazgranados, Nancy
    NIAAA, MD 20892 USA.
    Preston, Kenzie L.
    NIDA, MD 20892 USA; NIDA, MD 20892 USA.
    Herscovitch, Peter
    NIDA, MD 20892 USA.
    Tomasi, Dardo
    NIAAA, MD 20892 USA.
    Ramchandani, Vijay A.
    NIAAA, MD 20892 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Striatal Dopamine Release in Response to Morphine: A [C-11]Raclopride Positron Emission Tomography Study in Healthy Men2019In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 86, no 5, p. 356-364Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preclinical and human positron emission tomography studies have produced inconsistent results regarding the effects of opioids on mesolimbic dopamine (DA). Here, we quantify striatal DA release (measured by [C-11]raclopride displacement) in response to an intravenous infusion of morphine, and its relationship with morphine-induced subjective effects, in healthy, nondependent opioid-experienced participants. METHODS: Fifteen healthy male participants were initially included. Sessions were on separate days. On session 1, participants received intravenous morphine (10 mg/70 kg) in the clinic to ensure tolerability. Participants without adverse reactions (n = 10) then received intravenous morphine and placebo (saline) sessions, in counterbalanced order, while undergoing [C-11]raclopride positron emission tomography scans. Subjective and physiological responses were assessed. Region-of-interest and voxelwise image analyses were used to assess changes in [C-11]raclopride nondisplaceable binding potential. RESULTS: Morphine produced marked subjective and physiological effects and induced a significant decrease in [C-11]raclopride nondisplaceable binding potential, particularly in the nucleus accumbens and globus pallidus, where the change in [C-11]raclopride nondisplaceable binding potential was approximately 9%. However, the subjective effects of morphine did not show a simple pattern of correlation with DA release. CONCLUSIONS: This is, to our knowledge, the first study providing in vivo human evidence that DA transmission in the ventral striatum is affected by morphine. Further studies are required to fully delineate the DA contribution to the reinforcing effects of opioids.

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