Densitometrical analysis of opioid receptor ligand binding in the human striatum—I. Distribution of μ opioid receptor defines shell and core of the ventral striatum

Voorn, Pieter; Brady, Linda S.; Berendse, Henk W.; Richfield, Eric K.

doi:10.1016/0306-4522(96)00271-0

Cited by 76 publications

(83 citation statements)

References 62 publications

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“…Although repeated exposure to cocaine produces enduring increases in synaptic strength in both NAc shell and core, we recently demonstrated NAc synaptic plasticity following repeated amphetamine (22,24,(32)(33)(34), which raises a question of whether cocaine, rather than morphine, may be unusual in regards to plasticity in the NAc core. That said, given that the behavioral and neurochemical effects of opiates are dependent on activation of mu opioid receptors (2,35), the regional differences in morphine-induced plasticity demonstrated here may be related to the higher prevalence of mu opioid receptors in the NAc shell compared with the core (36,37).…”

Section: Prefer Test Pre-testmentioning

confidence: 99%

Reversal of morphine-induced cell-type–specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

Hearing

Jedynak

Ebner

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

142

169

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Drug-evoked plasticity at excitatory synapses on medium spiny neurons (MSNs) of the nucleus accumbens (NAc) drives behavioral adaptations in addiction. MSNs expressing dopamine D1 (D1R-MSN) vs. D2 receptors (D2R-MSN) can exert antagonistic effects in drugrelated behaviors, and display distinct alterations in glutamate signaling following repeated exposure to psychostimulants; however, little is known of cell-type-specific plasticity induced by opiates. Here, we find that repeated morphine potentiates excitatory transmission and increases GluA2-lacking AMPA receptor expression in D1R-MSNs, while reducing signaling in D2-MSNs following 10-14 d of forced abstinence. In vivo reversal of this pathophysiology with optogenetic stimulation of infralimbic cortexaccumbens shell (ILC-NAc shell) inputs or treatment with the antibiotic, ceftriaxone, blocked reinstatement of morphine-evoked conditioned place preference. These findings confirm the presence of overlapping and distinct plasticity produced by classes of abused drugs within subpopulations of MSNs that may provide targetable molecular mechanisms for future pharmacotherapies.opiates | nucleus accumbens | plasticity | GluA2-lacking AMPARs | ceftriaxone O pioid-based drugs are mainstays for pain management (1). However, side effects such as euphoria and the development of tolerance and dependence contribute to an increasing diversion of these readily available compounds for nontherapeutic use (2). Opioid agonist-based treatments are known to reduce some aspects of opioid addiction. On the other hand, these therapies often lead to high relapse rates when discontinued because they fail to eliminate key aspects of addiction such as conditioned associations that can trigger intense drug craving (2). Currently, development of alternative treatments for opioid addiction is hampered by a distinct lack of knowledge of the cellular plasticity that underlies persistent opioid-induced changes in behavior.The nucleus accumbens (NAc) region of the ventral striatum is involved in attribution of salience to drug-paired cues that can in turn motivate reward-related behavior (3, 4). Medium spiny neurons (MSNs), the principal cells of the NAc, are GABAergic projection neurons that receive coordinated glutamatergic afferents arising from several cortical and limbic brain regions (5, 6). MSNs are divided into two subpopulations based on expression of the dopamine receptor 1 (D1R-MSN) or dopamine receptor 2 (D2-MSN), with a small fraction (∼6-17%) expressing both receptors (7). Importantly, these subpopulations have divergent projection targets and exert antagonistic effects in rewardrelated behaviors (8).Long-lasting alterations in excitatory synaptic strength and glutamate release at MSNs produced by repeated exposure to drugs of abuse is a driving factor behind drug seeking and relapse (9-11). Numerous studies have examined effects of repeated psychostimulant exposure on synaptic strength and AMPA receptor (AMPAR)-mediated transmission in MSN subpopulations, with a majority of adaptati...

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Section: Prefer Test Pre-testmentioning

confidence: 99%

Reversal of morphine-induced cell-type–specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

Hearing

Jedynak

Ebner

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

142

169

View full text Add to dashboard Cite

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“…The patterns of distribution also appear to vary between species. The density and distribution of sites in the caudate and putamen of primates (Voorn et al, 1996), for example, demonstrate clear gradients of binding that are not evident in the rat, and the characteristic pattern of high-density patches in a low-density matrix readily observed in the rat is less evident in the human (Quirion et al, 1995;Voorn et al, 1996) and nonhuman primate (Porrino et al, 1991). These discrepancies suggest that findings regarding the anatomical distribution and function of the opioid system in the rodent may not always be relevant to the primate.…”

mentioning

confidence: 99%

Functional and anatomical localization of mu opioid receptors in the striatum, amygdala, and extended amygdala of the nonhuman primate

Daunais

Letchworth

Sim‐Selley

et al. 2001

J of Comparative Neurology

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The subregional distribution of mu opioid receptors and corresponding G-protein activation were examined in the striatum, amygdala, and extended amygdala of cynomolgus monkeys. The topography of mu binding sites was defined using autoradiography with [(3)H]DAMGO, a selective mu ligand. In adjacent sections, the distribution of receptor-activated G proteins was identified with DAMGO-stimulated guanylyl 5'(gamma-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding. Within the striatum, the distribution of [(3)H]DAMGO binding sites was characterized by a distinct dorsal-ventral gradient with a higher concentration of binding sites at more rostral levels of the striatum. [(3)H]DAMGO binding was further distinguished by the presence of patch-like aggregations within the caudate, as well as smaller areas of very dense receptor binding sites, previously identified in human striatum as neurochemically unique domains of the accumbens and putamen (NUDAPs). The amygdala contained the highest concentration of [(3)H]DAMGO binding sites measured in this study, with the densest levels of binding noted within the basal, accessory basal, paralaminar, and medial nuclei. In the striatum and amygdala, the distribution of DAMGO-stimulated G-protein activation largely corresponded with the distribution of mu binding sites. The central and medial nuclei of the amygdala, however, were notable exceptions. Whereas the concentration of [(3)H]DAMGO binding sites in the central nucleus of the amygdala was very low, the concentration of DAMGO-stimulated G-protein activation in this nucleus, as measured with [(35)S]GTPgammaS binding, was relatively high compared to other portions of the amygdala containing much higher concentrations of [(3)H]DAMGO binding sites. The converse was true in the medial nucleus, where high concentrations of binding sites were associated with lower levels of DAMGO-stimulated G-protein activation. Finally, [(3)H]DAMGO and [(35)S]GTPgammaS binding within the amygdala, particularly the medial nucleus, formed a continuum with the substantia innominata and bed nucleus of the stria terminalis, supporting the concept of the extended amygdala in primates.

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“…19 Although the 'core' and 'shell' subdivisions of the nucleus accumbens observed in rodent brain have yet to be defined absolutely in the human, this caudal portion of the nucleus accumbens probably contains both core and shell portions. 20,21 Quantitative immunoblotting Protein concentrations of the dopamine D1 and D2 receptors were determined by quantitative blot immunolabeling. Brain samples were homogenized in 100 volumes (w/v) Tris-HCl buffer (pH 7.5, 50 mM at 4°C) using a Brinkman polytron and centrifuged at 35 000 × g for 15 min.…”

Section: Brain Dissection For Neurochemical Analysesmentioning

confidence: 99%

Dopamine D1 receptor protein is elevated in nucleus accumbens of human, chronic methamphetamine users

et al. 2000

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Animal data have long suggested that an adaptive upregulation of nucleus accumbens dopamine D1 receptor function might underlie part of the dependency on drugs of abuse. We measured by quantitative immunoblotting protein levels of dopamine D1 and, for comparison, D2 receptors in brain of chronic users of methamphetamine, cocaine, and heroin. As compared with the controls, brain dopamine D1 receptor concentrations were selectively increased (by 44%) in the nucleus accumbens of the methamphetamine users, whereas a trend was observed in this brain area for reduced protein levels of the dopamine D2 receptor in all three drug groups (؊25 to ؊37%; P < 0.05 for heroin group only). Our data support the hypothesis that aspects of the drug-dependent state in human methamphetamine users might be related to increased dopamine D1 receptor function in limbic brain. Molecular Psychiatry (2000) 5, 664-672.

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Densitometrical analysis of opioid receptor ligand binding in the human striatum—I. Distribution of μ opioid receptor defines shell and core of the ventral striatum

Cited by 76 publications

References 62 publications

Reversal of morphine-induced cell-type–specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

Reversal of morphine-induced cell-type–specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

Functional and anatomical localization of mu opioid receptors in the striatum, amygdala, and extended amygdala of the nonhuman primate

Dopamine D1 receptor protein is elevated in nucleus accumbens of human, chronic methamphetamine users

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