Symposium 23 Tuesday Sept. 25th 9.00 am-10.30 am; Room: Lecture Hall 3: Alcohol, addiction and schizophrenia: Chairpersons: Heinz A (Germany), Kienast T (Germany)

• Published in: Alcohol and alcoholism (Oxford) Vol. 42; no. suppl 1; pp. i23 - i24
• Format: Journal Article
• Language: English
• Published: Oxford Oxford Publishing Limited (England) 01.08.2007
• ISSN: 0735-0414; 1464-3502
• DOI: 10.1093/alcalc/agm098

Presentation S23-1 Alcohol Dependence and fMRI Smolka MN, Leménager T, Vollmert C, Klein S, Klein O, Zimmer A, Heinz A, Mann K (Germany) Background. Cue reactivity paradigms are among the most prominent methods for investigating drug craving. Functional neuroimaging studies have adopted the traditional cue reactivity procedure to elucidate the neural bases of craving and relapse. Recent studies by our group investigated the effect of medications for relapse prevention on neuronal cue reactivity and the association of cue-induced brain activity with treatment outcome. Methods. Visual alcohol-related and control stimuli were presented in a block design during fMRI to assess brain activation. All participants were investigated twice, the first time after 2 to 3 weeks of abstinence, before start of study medication and a second time after 2 weeks on medication. Patients were treated with acamprosate, naltrexone or placebo in a double blind fashion. fMRI data were analyzed with SPM5. The level of significance was set to p< 0.001 in at lest 10 adjacent voxels. Results. Irrespective of medication cue-induced BOLD response decreased significantly in the ventral striatum and thalamus from session 1 to session 2. Differential effects of medication did not reach the predefined level of significance. However, the decrease of neuronal cue-reactivity in the right temporal inferior lobe and the right postcentral gyrus was more pronounced in patients assuming to receive verum compared to those assuming to receive placebo. Conclusions. Neuronal cue reactivity over a 2 weeks treatment period during early alcohol abstinence decreased irrespective of medication. Interestingly a substantial placebo effect in temporal and parietal areas was found. Therefore, the effects of natural recovery and placebo seem to be more pronounced than that of medication. Acknowledgements. This work was supported by the BMBF (Grant # 01EB0110-7 and 01EB0410-6). Presentation S23-2 Measuring the dopamine system Cumming P (Denmark) Presynapatic elements of monoamine innervations can be visualized using several PET tracers, with varying degrees of specificity for dopamine neurons. Vesicular monoamine transporters (VMAT2) can be labeled with [[sup]11C]dihydrotetrabenazine, and plasma membrane dopamine transporters (DAT) can be detected with labeled tropanes or with [[sup]11C]methylphenidate. The VMAT2 tracer has superior properties for detecting small reductions in the density of the dopamine innervation. Results obtained with DAT ligands must be qualified by the possibility of plasticity, such that reduced expression of DAT can accommodate reductions in VMAT2, which marks the density of innervation. However, this modulation of dopamine transporters must have consequences on the volume-transmission properties of dopamine signaling. FDOPA and related compounds are among the very few PET tracers for an enzyme activity, i.e. DOPA decarboxylase. The quantitation of FDOPA-PET has proven a considerable challenge, due to the large number of labeled species formed in plasma and in brain. Whereas the majority of studies have assumed irreversible trapping of [[sup]18F]fluorodopamine formed in brain, the progressive loss of labeled metabolites has definite consequences on the quantitation of FDOPA uptake. New methods allow a more appropriate steady-state analysis of FDOPA kinetics, in which are defined the intrinsic net FDOPA clearance to brain (K), the rate of washout of [[sup]18F]fluorodopamine (k[sub]loss), and their ratio, the steady-state distribution volume (V[sub]d). Normal aging is characterized by substantial increases in the magnitude of k[sub]loss in the presence of relatively stable K, presumably reflecting impaired transfer of [[sup]18F]fluorodopamine from the cytosol to a more secure vesicular compartment. Within a healthy population, there is considerable range in the relationship between K and k[sub]loss, suggesting a spectrum of individual modes of dopamine metabolism; some individuals have high K and low k[sub]loss (hoarders), whereas others have low K and high k[sub]loss (spendthrifts). We are investigating the relationship between these modes of operation and individual traits of cognition and personality. Patients with Parkinson's disease or schizophrenia have entirely distinct abnormalities in steady-state FDOPA kinetics, with the same net result; low v[sub]d. Thus, we have described schizophrenia as a circumstance of 'poverty in the midst of plenty'. Post-synaptic dopamine receptors can be studied with specific PET ligands. While D[sub]1 receptors are poorly investigated, D[sub]2-like receptors have attracted considerable attention, especially in the context of the in vivo competition model, which purports to reveal dynamic changes in the interstitial concentration of dopamine. However certain fundamental issues of this model are only now being addressed, with the advent of more specific ligands. For example, receptor agonist ligands seem to be more sensitive indicators of competition from dopamine in living brain than are antagonists such as [[sup]11C]raclopride. It is widely assumed that agonist binding sites (D[sub]2[sup]High) constitute a subset of the total number of sites in brain. However, this fundamental assumption is subject to caveats arising from methodological matters in the assay of receptors abundances in vitro. The maximal binding of dopamine receptor ligands in autoradiograms (200 nM) greatly exceeds the abundances measured by PET and in membrane preparations (20-30 nM), a finding which could suggest the presence of a large compartment of occult receptors in living brain. Presentation S23-3 Predictive neural coding of reward preference involves dissociable responses in human ventral midbrain and ventral striatum Dolan R (UK) How preferences are computed in the human brain is an important issue in relation to choice behaviour and decision making. One theoretical possibility is that preferences for rewards involve a dopaminergic signal that is expressed in the nigro-striatal pathway. I will present evidence that there is a dissociable pattern of response in preference judgements between VTA and striatum. Furthermore, I will present evidence that preferences and the computational processes that underpin acquisition of preference do not involve conscious access to the eliciting cue. Presentation S23-4 Behavioural theories and the neurophysiology of reward Schultz W (UK) The functions of rewards are based primarily on their effects on behavior and are less directly governed by the physics and chemistry of input events as in sensory systems. Therefore the investigation of neural mechanisms underlying reward functions requires behavioral theories that can conceptualize the different effects of rewards on behavior. The scientific investigation of behavioral processes by animal learning theory and economic utility theory has produced a theoretical framework which can help to elucidate the neural correlates for reward functions in learning, goal-directed approach behavior and decision-making under uncertainty. Individual neurons can be studied in the reward systems of the brain, including dopamine neurons, orbitofrontal cortex and striatum. The neural activity can be related to basic theoretical terms of reward and uncertainty, such as contiguity, contingency, prediction error, magnitude, probability, expected value and variance. Presentation S23-5 The dopamine system: Reward in alcohol addiction and schizophrenia Kienast T (Germany) Ventral and dorsal striatum receive dopaminergic neurofibres originating from the ventral tegmantal area. It has been shown that dopaminergic neurotransmission in straiatal brain regions interact with central processing of rewarding and reward-indicating stimuli and thus may affect fronto-cortical-striatal-thalamic circuits regulating goal-directed behavior. Neuropsychiatric disorders such as alcohol addiction and schizophrenia show a dysfunction of dopaminergic neurotransmission. As we know from clinical observations of both groups, those suffering either from alcohol addiction or from schizophrenia show a disturbed motivation pattern concerning their appetitive behavior towards rewarding stimuli. The neurobiological correlate for this observation may be found in the ventral striatum or nucleus accumbens. Alcohol stimulates dopamine release in the ventral striatum and particularly in the nucleus accumbens and thus reinforces alcohol consumption. There is also evidence of down-regulated dopamine D2 receptors in this brain area that may be a homeostatic reaction. This finding has been associated with alcohol craving and an increase in the processing of alcohol-related stimuli in the medial prefrontal cortex. In schizophrenia brain imaging studies in which intrasynaptic dopamine release had been manipulated in vivo have shown that increased subcortical dopamine release is associated with the pathogenesis of positive symptoms in schizophrenia. Finally these observations indicate that in both, alcoholism and schizophrenia exists a dysfunction of the dopamine neurotransmission that may be associated with motivational deficits and a disturbed reaction pattern on reinforcing stimuli.