NR2B subunit of NMDA receptor at nucleus accumbens is involved in morphine rewarding effect by siRNA study

Kao, Jen-Hsin; Huang, Eagle Yi‐Kung; Tao, Pao‐Luh

doi:10.1016/j.drugalcdep.2011.04.019

Cited by 29 publications

(18 citation statements)

References 43 publications

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“…Direct infusion of ifenprodil or GluN2B-specific small interfering RNA (siRNA) into the NAcore inhibits cue-induced and drug-primed heroin seeking . Similarly, infusion of GluN2B-specific siRNA into the NAshell inhibits morphine CPP (Kao et al, 2011), whereas infusion of GluN2B-specific siRNA into the NAcore inhibits cueand drug-induced heroin seeking . These data illustrate the importance of the GluN2B-containing NMDAR subtype in mediating accumbens glutamatergic plasticity that underlies opiate reward and drug seeking.…”

Section: B N-methyl-d-aspartate Receptorsmentioning

confidence: 99%

The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis

et al. 2016

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Section: B N-methyl-d-aspartate Receptorsmentioning

confidence: 99%

The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis

et al. 2016

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“…The BLA potentiates shell neuronal activity in part via stimulation of NMDA-Rs (Floresco et al 1998;Floresco et al 2001). NMDA-R antagonists applied to the nucleus accumbens disrupt the acquisition, expression, and reinstatement of morphine CPP (Popik and Kolasiewicz 1999;Ma et al 2007;Kao et al 2011), at least in part through NR2B-containing NMDA-Rs (Fig. 1b) Kao et al 2011).…”

Section: Amygdala Outputsmentioning

confidence: 99%

“…NMDA-R antagonists block both the acquisition and expression of morphine CPP (Tzschentke and Schmidt 1995;Tzschentke and Schmidt 1997;Popik et al 1998Popik et al , 2003aSuzuki et al 2000;Papp et al 2002;Ribeiro Do Couto et al 2004;Yonghui et al 2006;Rezayof et al 2007;Zarrindast et al 2007;Heinmiller et al 2009;Kao et al 2011;Ma et al 2011b). These effects are at least partly mediated by NR2B-containing NMDA-Rs, as NR2B-selective antagonists, such as ifenprodil, are capable of producing comparable effects (Suzuki et al 1999;Narita et al 2000;Ma et al 2006Ma et al , 2011b.…”

Section: Conditioned Reward and Aversionmentioning

confidence: 99%

“…NMDA-R antagonists applied to the nucleus accumbens disrupt the acquisition, expression, and reinstatement of morphine CPP (Popik and Kolasiewicz 1999;Ma et al 2007;Kao et al 2011), at least in part through NR2B-containing NMDA-Rs (Fig. 1b) Kao et al 2011). Gene transfer of the glutamate transporter (glutamate transporter 1 [EAAT2] [GLT-1]) to the shell also blocks the acquisition of CPP (Fig.…”

Section: Amygdala Outputsmentioning

confidence: 99%

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Glutamate Mechanisms Underlying Opiate Memories

Peters

Vries

2012

Cold Spring Harbor Perspectives in Medicine

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Correspondence: tj.devries@vumc.nlAs the major excitatory neurotransmitter in the brain, glutamate plays an undisputable integral role in opiate addiction. This relates, in part, to the fact that addiction is a disorder of learning and memory, and glutamate is required for most types of memory formation. As opiate addiction develops, the addict becomes conditioned to engage in addictive behaviors, and these behaviors can be triggered by opiate-associated cues during abstinence, resulting in relapse. Some medications for opiate addiction exert their therapeutic effects at glutamate receptors, especially the NMDA receptor. Understanding the neural circuits controlling opiate addiction, and the locus of glutamate's actions within these circuits, will help guide the development of targeted pharmacotherapeutics for relapse.

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“…Accumulating evidence suggests that NMDARs, particularly those containing the NR2B subunit, play a crucial role in opioid addiction [44]. Chronic exposure to morphine markedly decreases the expression of the NR2B subunit in the nucleus accumbens [45], frontal cortex, and striatum [45]. In rat hippocampus and hypothalamus, chronic morphine treatment fails to affect the allosteric binding but significantly decreases the expression of NR2B [46][47][48].…”

Section: Discussionmentioning

confidence: 99%

Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats

Wang¹,

Zhao

et al. 2016

Neurosci. Bull.

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Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hippocampal extracellular glutamate level induced by naloxone (2 mg/kg, i.p.) precipitation. Agmatine (20 mg/kg, s.c.) administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synaptosomes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agmatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors (NMDARs) was downregulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine prevented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including modulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.

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NR2B subunit of NMDA receptor at nucleus accumbens is involved in morphine rewarding effect by siRNA study

Cited by 29 publications

References 43 publications

The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis

The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis

Glutamate Mechanisms Underlying Opiate Memories

Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats

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