Local μ-Opioid Receptor Antagonism Blunts Evoked Phasic Dopamine Release in the Nucleus Accumbens of Rats

Gómez-A, Alexander; Shnitko, Tatiana A.; Barefoot, Haley M.; Brightbill, Eleanor L.; Sombers, Leslie A.; Nicola, Saleem M.; Robinson, Donita L.

doi:10.1021/acschemneuro.8b00437

Cited by 9 publications

(6 citation statements)

References 64 publications

(103 reference statements)

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“…In contrast, DOR activation generally increases DA release in the NAc through circuit interactions potentially involving inhibition of KOR signaling ( Svingos et al, 1999 ). MORs are the majority of cell types in the NAc and their activation can increase or decrease NAc DA release through a variety of direct and indirect actions ( Britt and McGehee, 2008 ; Gomez et al, 2019 ).…”

Section: Da Signaling In the Nacmentioning

confidence: 99%

Endocannabinoid Modulation of Nucleus Accumbens Microcircuitry and Terminal Dopamine Release

Covey

Yocky

2021

Front. Synaptic Neurosci.

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The nucleus accumbens (NAc) is located in the ventromedial portion of the striatum and is vital to valence-based predictions and motivated action. The neural architecture of the NAc allows for complex interactions between various cell types that filter incoming and outgoing information. Dopamine (DA) input serves a crucial role in modulating NAc function, but the mechanisms that control terminal DA release and its effect on NAc neurons continues to be elucidated. The endocannabinoid (eCB) system has emerged as an important filter of neural circuitry within the NAc that locally shapes terminal DA release through various cell type- and site-specific actions. Here, we will discuss how eCB signaling modulates terminal DA release by shaping the activity patterns of NAc neurons and their afferent inputs. We then discuss recent technological advancements that are capable of dissecting how distinct cell types, their afferent projections, and local neuromodulators influence valence-based actions.

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Section: Da Signaling In the Nacmentioning

confidence: 99%

Endocannabinoid Modulation of Nucleus Accumbens Microcircuitry and Terminal Dopamine Release

Covey

Yocky

2021

Front. Synaptic Neurosci.

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“…The widely supported mechanism through which opioids increase striatal dopamine is via disinhibition of VTA dopamine neurons through MOR‐mediated inhibition of GABA neurons in the rostromedial tegmental nucleus 18,20,21,81,82 . However, there is also evidence that opioids can act locally in the NAc to influence dopamine transmission, with local NAc infusion of fentanyl increasing, and MOR antagonist decreasing, dopamine levels 22,83 . To initially investigate the effects of oxycodone on dopamine transmission in the NAc, we applied oxycodone directly to NAc slices.…”

Section: Discussionmentioning

confidence: 99%

“…18,20,21,81,82 However, there is also evidence that opioids can act locally in the NAc to influence dopamine transmission, with local NAc infusion of fentanyl increasing, and MOR antagonist decreasing, dopamine levels. 22,83 To initially investigate the effects of oxycodone on dopamine transmission in the NAc, we applied oxycodone directly to NAc slices. We found that oxycodone induced a robust MOR-dependent reduction in dopamine uptake, which to our knowledge has not been reported previously.…”

Section: Local Actions Of Oxycodone Reduce Dopamine Uptake In the Nac...mentioning

confidence: 99%

Intermittent access to oxycodone decreases dopamine uptake in the nucleus accumbens core during abstinence

Samson

Kortagere

et al. 2022

Addiction Biology

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A major obstacle in treating opioid use disorder is the persistence of drug seeking or craving during periods of abstinence, which is believed to contribute to relapse. Dopamine transmission in the mesolimbic pathway is posited to contribute to opioid reinforcement, but the processes by which dopamine influences drug seeking have not been completely elucidated. To examine whether opioid seeking during abstinence is associated with alterations in dopamine transmission, female and male rats self‐administered oxycodone under an intermittent access schedule of reinforcement. Following self‐administration, rats underwent a forced abstinence period, and cue‐induced seeking tests were conducted to assess oxycodone seeking. One day following the final seeking test, rats were sacrificed to perform ex vivo fast scan cyclic voltammetry and western blotting in the nucleus accumbens. Rats displayed reduced dopamine uptake rate on abstinence day 2 and abstinence day 15, compared to oxycodone‐naïve rats. Further, on abstinence day 15, rats had reduced phosphorylation of the dopamine transporter. Additionally, local application of oxycodone to the nucleus accumbens reduced dopamine uptake in oxycodone‐naïve rats and in rats during oxycodone abstinence, on abstinence day 2 and abstinence day 15. These observations suggest that abstinence from oxycodone results in dysfunctional dopamine transmission, which may contribute to sustained oxycodone seeking during abstinence.

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“…Electron microscopy in rodents have suggested that striatal KOR expression is predominantly presynaptic (Meshul & McGinty, 2000), where KOR directly affect DA release (Britt & McGehee, 2008; Clark & Abi‐Dargham, 2019; Werling et al, 1988; Yamada et al, 2006). In contrast, striatal MOR (a main contributor to opioid reward and locomotor effects) is predominantly expressed on GABAergic neurons and interneurons which, among other functions, may indirectly affect DA release (Charbogne et al, 2017; Cui et al, 2014; Gómez‐A et al, 2019). KOR availability accounted for a unique part of variance in striatal patterns of NAL‐ and MRP‐DA release (Figure 4b) which could be consistent with its direct effect on DA terminals whereas striatal MOR availability (measured with PET) may reflect contributions from multiple MOR functions.…”

Section: Discussionmentioning

confidence: 99%

Brain opioid segments and striatal patterns of dopamine release induced by naloxone and morphine

Shokri‐Kojori

Naganawa

Ramchandani

et al. 2021

Human Brain Mapping

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Opioid receptors are expressed throughout the brain and play a major role in regulating striatal dopamine (DA) release. Clinical studies have shown that naloxone (NAL, a nonspecific opioid antagonist) in individuals with opioid use disorder and morphine (MRP, a nonspecific opioid agonist) in healthy controls, resulted in DA release in the dorsal and ventral striatum, respectively. It is not known whether the underlying patterns of striatal DA release are associated with the striatal distribution of opioid receptors. We leveraged previously published PET datasets (collected in independent cohorts) to study the brain‐wide distribution of opioid receptors and to compare striatal opioid receptor availability with striatal DA release patterns. We identified three major gray matter segments based on availability maps of DA and opioid receptors: striatum, and primary and secondary opioid segments with high and intermediate opioid receptor availability, respectively. Patterns of DA release induced by NAL and MRP were inversely associated and correlated with kappa (NAL: r(68) = −0.81, MRP: r(68) = 0.54), and mu (NAL: r(68) = −0.62, MRP: r(68) = 0.46) opioid receptor availability. Kappa opioid receptor availability accounted for a unique part of variance in NAL‐ and MRP‐DA release patterns (ΔR2 >0.14, p <.0001). In sum, distributions of opioid receptors distinguished major cortical and subcortical regions. Patterns of NAL‐ and MRP‐induced DA release had inverse associations with striatal opioid receptor availability. Our approach provides a pattern‐based characterization of drug‐induced DA targets and is relevant for modeling the role of opioid receptors in modulating striatal DA release.

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Local μ-Opioid Receptor Antagonism Blunts Evoked Phasic Dopamine Release in the Nucleus Accumbens of Rats

Cited by 9 publications

References 64 publications

Endocannabinoid Modulation of Nucleus Accumbens Microcircuitry and Terminal Dopamine Release

Endocannabinoid Modulation of Nucleus Accumbens Microcircuitry and Terminal Dopamine Release

Intermittent access to oxycodone decreases dopamine uptake in the nucleus accumbens core during abstinence

Brain opioid segments and striatal patterns of dopamine release induced by naloxone and morphine

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