Biological substrates of addiction

Joffe, Max E.; Grueter, Carrie A.; Grueter, Brad A.

doi:10.1002/wcs.1273

Cited by 30 publications

(32 citation statements)

References 176 publications

(265 reference statements)

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“…Since depressive symptoms are often comorbid with drug abuse and addiction (Joffe et al, 2014; Volkow, 2010), we assessed behavioral despair in two parallel assays, the TST and the FST. Due to previously observed genotype-sex interactions in these behaviors (Kokras and Dalla, 2014) we ran separate cohorts of male and female mice.…”

Section: Discussionmentioning

confidence: 99%

“…Adaptations involved in the development of addiction-like behaviors share common mechanisms with learning and memory processes (Grueter et al, 2012; Joffe et al, 2014; Koob and Volkow, 2010; Lüscher and Malenka, 2011). In particular, N-methyl-D-aspartate receptors (NMDARs) have been extensively studied as mediators of drug experience-dependent memory formation (Brown et al, 2011; Kalivas and Alesdatter, 1993; Karler et al, 1989; Wolf and Khansa, 1991; Zweifel LS, Argilli E, Bonci A, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…One key brain complex that subserves reward-related behaviors is the striatum, which is conceptualized as a gatekeeper of descending neurotransmission relating to motor control, reward, and reinforcement (Grueter et al, 2012; Joffe et al, 2014; Kreitzer and Malenka, 2008). Throughout the dorsal and ventral striatum, GABAergic medium spiny neurons (MSNs) comprise 90–95% of neurons and provide the output from the structures.…”

Section: Introductionmentioning

confidence: 99%

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GluN1 deletions in D1- and A2A-expressing cell types reveal distinct modes of behavioral regulation

2017

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N-methyl-D-aspartate receptors (NMDARs) are profound regulators of glutamate neurotransmission and behavior. To coordinate components of the limbic system, the dorsal and ventral striatum integrate cognitive and emotional information towards the execution of complex behaviors. Striatal outflow is conveyed by medium spiny neurons (MSNs), which can be dichotomized by expression of dopamine receptor subtype 1 (D1) or adenosine receptor subtype 2A (A2A). To examine how striatal NMDAR function modulates reward-related behaviors, we generated D1- and A2A-specific genetic deletions of the obligatory GluN1 subunit. Interestingly, we observed no differences in any GluN1−/− genotype in reward learning as assessed by acquisition or extinction of cocaine conditioned place preference (CPP). Control and A2A-GluN−/− mice exhibited robust cocaine-primed reinstatement, however this behavior was markedly absent in D1-GluN−/− mice. Interestingly, dual D1-/A2A-GluN−/− mice displayed an intermediate reinstatement phenotype. Next, we examined models of exploration, anxiety, and despair, states often associated with relapse to addiction-related behavior, to determine NMDAR contribution in D1 and A2A cell types to these behaviors. D1-GluN1−/− mice displayed aberrant exploratory locomotion in a novel environment, but the phenotype was absent in dual D1/A2A-GluN1−/− mice. In contrast A2A-GluN1−/− mice displayed a despair-resistant phenotype, and this phenotype persisted in dual D1/A2A-GluN−/− mice. These data support the hypothesis that cell type-specific NMDAR signaling regulates separable behavioral outcomes related to locomotion, despair, and relapse.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GluN1 deletions in D1- and A2A-expressing cell types reveal distinct modes of behavioral regulation

2017

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“…psychosoziale Stressoren, wie Bindungstraumatisierungen, die Funktionen des zentralen Stressbewältigungssystems beeinträchtigen, sodass bei Menschen mit Abhängigkeitserkrankun-gen von veränderten Stressaktivitäten und Stressantworten ausgegangen werden kann [17,18]. Einerseits führt die Sucht erkrankung selbst durch den Wechsel von Intoxikationen und Suchtmittelentzügen zu einer Labilisierung des Stressverarbeitungssystems, andererseits gibt es hohe Komorbiditätsraten in Bezug auf affektive Störungen, BorderlinePersönlichkeitsstö-rungen und Traumafolgestörungen [19].…”

Section: Zwischenmenschliche Fertigkeitenunclassified

DBT in der Suchtbehandlung: Das Göttinger Modell

2015

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DBT in der Suchtbehandlung: Das Göttinger Modell DBT in Addiction Treatment: The Göttingen ModelTherapiemethoden sich als viel zu mobilisierend erwiesen, zeigte sich klassische Verhaltenstherapie zu wenig validierend und zu konfrontativ.Die DBT ist eine kognitiv-behavioral orientierte Therapieform, die gleichzeitig Akzeptanz für dysfunktionales Verhalten chronischer psychischer Störungen und dessen Veränderung bewirkt. Die DBT wurde ursprünglich zur Behandlung von Borderline-Persönlichkeitsstörungen entwickelt.In der DBT hat M. Linehan die klassische Verhaltenstherapie durch die Einführung von Akzeptanz und Dialektik grundlegend verändert. Dialektik ist eine sehr alte Form der Wahrheitsfindung: Widersprüche werden auf einer höheren Ebene verknüpft, um zu mehr Wahrheitsgehalt zu gelangen. Dialektik in der DBT bedeutet, Symptome, Schwierigkeiten, Einschränkungen und Dialektisch-behaviorale Therapie nach Marsha Linehan ▼ Die dialektisch-behaviorale Therapie (DBT) wurde in den 80er Jahren von Marsha Linehan als ambulantes psychotherapeutisches Verfahren zur Behandlung chronisch suizidaler Frauen mit einer Borderline-Persönlichkeitsstörung entwickelt [1]. DBT ist eine kognitiv-behavioral orientierte Therapieform, ergänzt um Elemente aus humanistischen und körperorientierten Therapieverfahren wie der Sozialpsychologie, Hypnound Gestalttherapie und des Zen-Buddhismus. Grund für die Entwicklung der DBT war die Feststellung, dass diese psychisch schwer gestörte Patientengruppe mit den damaligen psychotherapeutischen Behandlungsmethoden, wie psychodynamischer Therapie oder klassischer Verhaltenstherapie nicht zu behandeln waren. Zusammenfassung ▼Die dialektisch-behaviorale Therapie (DBT) hat sich unter Einbeziehung suchtspezifischer Symptomatik als eine ergänzende Therapiemethode in der Suchtbehandlung klinisch gut bewährt. Craving und unkontrollierter Suchtmittelkonsum als Kernsymptome in der Behandlung von Abhän-gigkeitserkrankungen fanden in der ursprüngli-chen Form der dialektisch-behavioralen Therapie nach Marsha Linehan wenig Berücksichtigung. Deshalb wurde das DBT-Konzept an die Suchterkrankung adaptiert und das gesamte Manual des Skillstrainings speziell zur Besserung der suchtspezifischen dysfunktionalen Verhaltensweisen überarbeitet und erweitert: Das Göttin-ger Modell. Dieser Beitrag befasst sich mit der Entwicklung und Vorstellung dieses DBT-Konzeptes integriert in konventionelle Konzepte einer Suchtabteilung an einem psychiatrischen Fachkrankenhaus mit Versorgungsauftrag. Abstract ▼

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“…A principal objective in neuroscience is to understand the molecular mechanisms by which neurons and muscles respond to neurotransmitters. This objective is important to advance our basic science understanding of the brain, but also is of great medical significance since many pharmaceuticals used to treat psychiatric disorders act by mimicking, antagonizing, or altering the levels of naturally-occurring neurotransmitters (Conn and Roth, 2008: PMID 18216778), and drugs of abuse also act by altering neurotransmitter signaling (Joffe et al, 2014: PMID 24999377).…”

Section: Introductionmentioning

confidence: 99%

Neurotransmitter signaling through heterotrimeric G proteins: insights from studies in C. elegans

Koelle

2018

WormBook

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Neurotransmitters signal via G protein coupled receptors (GPCRs) to modulate activity of neurons and muscles. C. elegans has ~150 G protein coupled neuropeptide receptor homologs and 28 additional GPCRs for small-molecule neurotransmitters. Genetic studies in C. elegans demonstrate that neurotransmitters diffuse far from their release sites to activate GPCRs on distant cells. Individual receptor types are expressed on limited numbers of cells and thus can provide very specific regulation of an individual neural circuit and behavior. G protein coupled neurotransmitter receptors signal principally via the three types of heterotrimeric G proteins defined by the G alpha subunits Gαo, Gαq, and Gαs. Each of these G alpha proteins is found in all neurons plus some muscles. Gαo and Gαq signaling inhibit and activate neurotransmitter release, respectively. Gαs signaling, like Gαq signaling, promotes neurotransmitter release. Many details of the signaling mechanisms downstream of Gαq and Gαs have been delineated and are consistent with those of their mammalian orthologs. The details of the signaling mechanism downstream of Gαo remain a mystery. Forward genetic screens in C. elegans have identified new molecular components of neural G protein signaling mechanisms, including Regulators of G protein Signaling (RGS proteins) that inhibit signaling, a new Gαq effector (the Trio RhoGEF domain), and the RIC-8 protein that is required for neuronal Gα signaling. A model is presented in which G proteins sum up the variety of neuromodulator signals that impinge on a neuron to calculate its appropriate output level.

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Biological substrates of addiction

Cited by 30 publications

References 176 publications

GluN1 deletions in D1- and A2A-expressing cell types reveal distinct modes of behavioral regulation

GluN1 deletions in D1- and A2A-expressing cell types reveal distinct modes of behavioral regulation

DBT in der Suchtbehandlung: Das Göttinger Modell

Neurotransmitter signaling through heterotrimeric G proteins: insights from studies in C. elegans

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