The Neurobiology of Opiate Motivation

Ting‐A‐Kee, Ryan; Kooy, Derek van der

doi:10.1101/cshperspect.a012096

Cited by 45 publications

(21 citation statements)

References 124 publications

(173 reference statements)

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“…These lesions do, however, result in at least some loss of PPTg glutamatergic and GABAergic neurons in addition to almost complete loss of cholinergic neurons. Accordingly, the PPTg has been suggested to be part of a DA-independent mechanism, likely involving its descending projections (Heinmiller et al, 2009), important for opioid reward in drug-naïve animals (Bechara et al, 1998; Nader et al, 1997; Ting-A-Kee and van der Kooy, 2012). Dorsal tegmental outputs become less important for opioid CPP and self-administration after opioid dependence and withdrawal while DA output becomes more important (Bechara and van der Kooy, 1989; Bechara et al, 1998; 1992; Laviolette and van der Kooy, 2001; Laviolette et al, 2004; Nader and van der Kooy; 1997; Nader et al, 1997; 1994; Vargas-Perez et al, 2009; 2007; Ting-A-Kee and van der Kooy, 2012).…”

Section: Acetylcholine Glutamate and Opioidsmentioning

confidence: 99%

Opioid-induced rewards, locomotion, and dopamine activation: A proposed model for control by mesopontine and rostromedial tegmental neurons

Steidl

Wasserman

Blaha

et al. 2017

Neuroscience & Biobehavioral Reviews

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Opioids, such as morphine or heroin, increase forebrain dopamine (DA) release and locomotion, and support the acquisition of conditioned place preference (CPP) or self-administration. The most sensitive sites for these opioid effects in rodents are in the ventral tegmental area (VTA) and rostromedial tegmental nucleus (RMTg). Opioid inhibition of GABA neurons in these sites is hypothesized to lead to arousing and rewarding effects through disinhibition of VTA DA neurons. We review findings that the laterodorsal tegmental (LDTg) and pedunculopontine tegmental (PPTg) nuclei, which each contain cholinergic, GABAergic, and glutamatergic cells, are important for these effects. LDTg and/or PPTg cholinergic inputs to VTA mediate opioid-induced locomotion and DA activation via VTA M5 muscarinic receptors. LDTg and/or PPTg cholinergic inputs to RMTg also modulate opioid-induced locomotion. Lesions or inhibition of LDTg or PPTg neurons reduce morphine-induced increases in forebrain DA release, acquisition of morphine CPP or self-administration. We propose a circuit model that links VTA and RMTg GABA with LDTg and PPTg neurons critical for DA-dependent opioid effects in drug-naïve rodents.

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Section: Acetylcholine Glutamate and Opioidsmentioning

confidence: 99%

Opioid-induced rewards, locomotion, and dopamine activation: A proposed model for control by mesopontine and rostromedial tegmental neurons

Steidl

Wasserman

Blaha

et al. 2017

Neuroscience & Biobehavioral Reviews

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“…Although heroin and other opioid agonists act on opioid receptors, preclinical evidence supports involvement of the GABA system in their effects ( Zetterström and Fillenz, 1990 , Finlay et al, 1992 and Creed et al, 2014 ). Endorphins or mu opiate agonists inhibit GABA-ergic tonic inhibition of dopamine neuronal activity in the ventral tegmental area (VTA) resulting in increased dopamine neuronal firing and may thus contribute to the desire or compulsion to use opiates ( Johnson and North, 1992 and Ting-A-Kee and van der Kooy, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Using [11C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism

et al. 2016

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The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [11C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [11C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [11C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [11C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n = 12) underwent an [11C]Ro15 4513 PET scan and compared with matched healthy controls (n = 13). We found a significant reduction in [11C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [11C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [11C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [11C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates.

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“…So scheinen opioiderge Belohnungseffekte bei opiatnaiven Tieren vorrangig durch absteigende Projektionen aus der VTA in den Hirnstamm und in tegmentale pedunculopontine Kerngebiete vermittelt zu werden. Bei längerem oder wiederholtem Gebrauch werden die motivationalen Effekte von Opioiden hingegen über die aus der VTA aufsteigenden Bahn in den dopaminergen Nacc (40). Diese Hypothese wird gestützt durch tierexperimentelle Untersuchungen, die zeigen konnten, dass die durch Opiate CPP bei opiatnaiven Ratten durch die Gabe von Dopaminrezeptorantagonisten nicht aufgehoben wird.…”

Section: Opioide Und Dopaminunclassified

Belohnung und das Opioidsystem

Rau¹,

Malejko²,

Graf³

2018

Nervenheilkunde

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ZusammenfassungDie Aussicht auf Belohnung ist eine fundamentale Motivation menschlichen Verhaltens und beeinflusst eine Vielzahl neurokognitiver Funktionen wie zielgerichtetes Verhalten und Lernen. Motivationales Verhalten wird im mesolimbischem Belohnungssystem maßgeblich durch den Neurotransmitter Dopamin moduliert. Eine Vielzahl tierexperimenteller und humaner Untersuchungen belegen jedoch eine Interaktion zwischen dem dopaminergen Belohnungssystem und Opioidsystem. Hinsichtlich der opioidergen Modulation des dopaminergen Belohnungssystems sind neben μ-Opioidrezeptoren und dopaminergen Neurone, auch GABAerge und glutamaterge Mechanismen relevant. In diesem Artikel sollen grundlegende Mechanismen der Interaktion zwischen dem Opioid- und dopaminergen Belohnungssystem vorgestellt werden. Das Verständnis dieser Interaktionen ist nicht nur in grundlagenwissenschaftlicher, sondern auch in klinischer Hinsicht relevant und soll am Beispiel des Opioidrezeptorantagonisten Naltrexon als medikamentöse Rückfallprophylaxe beim Alkoholabhängigkeitssyndrom und anhand der Verhaltenseffekte auf die Verarbeitung primärer Verstärker wie Nahrung dargestellt werden.

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The Neurobiology of Opiate Motivation

Cited by 45 publications

References 124 publications

Opioid-induced rewards, locomotion, and dopamine activation: A proposed model for control by mesopontine and rostromedial tegmental neurons

Opioid-induced rewards, locomotion, and dopamine activation: A proposed model for control by mesopontine and rostromedial tegmental neurons

Using [11C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism

Belohnung und das Opioidsystem

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