Effect of Precipitated Withdrawal on Extracellular Glutamate and Aspartate in the Nucleus Accumbens of Chronically Morphine-Treated Rats: An In Vivo Microdialysis Study

Sepúlveda, Milena; Hernández, Luis Felipe Álvarez; Rada, Pedro; Tucci, Sonia; Contreras, Enrique

doi:10.1016/s0091-3057(97)00550-9

Cited by 72 publications

(39 citation statements)

References 28 publications

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“…These studies have assessed various classical somatic and autonomic signs of withdrawal, as well as biochemical markers (Bristow et al, 1997;Rasmussen, 1995). Ability of NMDA receptor antagonists to block the expression of opioid withdrawal is consistent with the frequently reported increase in glutamate release in opioid-withdrawn animals (Sepulveda et al, 1998) and facilitation of the withdrawal signs by glutamate receptor agonist administration (Tokuyama et al, 1996). Similarly, stimulation of mGluRII receptors with (+)-2-aminobicyclo [3,1,0] hexane-2,6-dicarboxylic acid (LY354740) was shown to inhibit the expression of morphine dependence (Klodzinska et al, 1999;Vandergriff and Rasmussen, 1999).…”

Section: Effects Of Gcp II Inhibition On Morphine Dependence/ Withdrawalsupporting

confidence: 66%

“…If this hypothesis were correct, it could be speculated that administration of a high dose (100 mg/kg) of 2-PMPA leads to high concentrations of NAAG that acts as an agonist, rather than an antagonist at NMDA receptors, and thus increases the severity of morphine withdrawal. In support, it should be noted that during opioid withdrawal there is a massive release of glutamate (Rasmussen, 1995;Jhamandas et al, 1996;Sepulveda et al, 1998). The effects of massive glutamate release apparently may not be prevented by NAAG-induced mGluRII stimulation and/or a decrease in glutamate release.…”

Section: Effects Of Gcp II Inhibition On Morphine Dependence/ Withdrawalmentioning

confidence: 96%

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Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Popik

Kozela

Wróbel

et al. 2002

Neuropsychopharmacol

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Inhibition of glutamate carboxypeptidase II (GCP II; NAALADase) produces a variety of effects on glutamatergic neurotransmission. The aim of this study was to investigate effects of GCP II inhibition with the selective inhibitor, 2-PMPA, on: (a) development of tolerance to the antinociceptive effects, (b) withdrawal, and (c) conditioned reward produced by morphine in C57/Bl mice. The degree of tolerance was assessed using the tail-flick test before and after 6 days of twice daily (b.i.d.) administration of 2-PMPA and 10 mg/kg of morphine. Opioid withdrawal was measured 3 days after twice daily morphine (30 or 10 mg/kg) administration, followed by naloxone challenge. Conditioned morphine reward was investigated using conditioned place preference with a single morphine dose (10 mg/kg). High doses of 2-PMPA inhibited the development of morphine tolerance (resembling the effect of 7.5 mg/kg of the NMDA receptor antagonist, memantine) while not affecting the severity of withdrawal. A high dose of 2-PMPA (100 mg/kg) also significantly potentiated morphine withdrawal, but inhibited both acquisition and expression of morphine-induced conditioned place preference. Memantine inhibited the intensity of morphine withdrawal as well as acquisition and expression of morphine-induced conditioned place preference. In addition, 2-PMPA did not affect learning or memory retrieval in a simple two-trial test, nor did it produce withdrawal symptoms in morphinedependent, placebo-challenged mice. Results suggest involvement of GCP II (NAALADase) in phenomena related to opioid addiction.

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Section: Effects Of Gcp II Inhibition On Morphine Dependence/ Withdrawalsupporting

confidence: 66%

Section: Effects Of Gcp II Inhibition On Morphine Dependence/ Withdrawalmentioning

confidence: 96%

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Popik

Kozela

Wróbel

et al. 2002

Neuropsychopharmacol

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“…Both PKA and glutamate-mediated increases in Ca 2ϩ are necessary for CREB activation, but only PKA can induce GluR1 phosphorylation at Ser 845 (Sheng et al, 1991;Chao et al, 2002a). Thus, naloxone-induced P-CREB in morphine-dependent rats might reflect synergism between signaling from withdrawal-induced glutamate release (Sepulveda et al, 1998) and increased cAMP. Other studies have shown that low doses of naloxone induce c-fos and Fos-related antigens (FRAs) in the NAc of morphinedependent rats (Walters et al, 2000;Gracy et al, 2001).…”

Section: Dissociation Of Motivational and Somatic Withdrawal Signsmentioning

confidence: 99%

“…SKF 82958 increased P-GluR1 selectively in the NAc of morphine-dependent rats, but the D 1 receptor-mediated increase in P-GluR1 was significantly reduced in dependent rats treated with naloxone. P-GluR1 is rapidly dephosphorylated during AMPA receptor activation in the NAc (Snyder et al, 2003); because glutamate release is increased in the NAc during morphine withdrawal (Sepulveda et al, 1998), a concomitant increase in AMPA receptor activation and GluR1 dephosphorylation would be expected. It is thus possible that the rewarding effects of SKF 82958 observed in morphine-dependent rats and those treated with naloxone are mediated in different brain regions.…”

Section: Mechanisms Of D 1 Agonist Effects In Morphine-dependent Ratsmentioning

confidence: 99%

Behavioral and Molecular Effects of Dopamine D1 Receptor Stimulation during Naloxone-Precipitated Morphine Withdrawal

Chartoff

Mague

Barhight

et al. 2006

Journal of Neuroscience

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Morphine dependence is characterized by somatic and motivational signs of withdrawal that likely contribute to the maintenance of addictive behavior. The nucleus accumbens (NAc) receives extensive dopaminergic input and is an important substrate for mediating these aversive states. In the NAc, the function of the transcription factor cAMP response element binding protein (CREB) and AMPA glutamate receptor subunit, type 1 (GluR1) can be regulated by dopamine (DA) D 1 receptor-mediated phosphorylation (P-CREB, P-GluR1). However, the roles of D 1 receptors, CREB, and GluR1 in morphine dependence are not well understood. Here, we show that somatic signs of naloxone-precipitated withdrawal were associated with increased P-CREB, but not P-GluR1, in the NAc of morphinedependent rats. The D 1 receptor agonist chloro-APB hydrobromide (SKF 82958) was rewarding in morphine-dependent rats and blocked naloxone-induced place aversions and somatic signs of withdrawal. Surprisingly, SKF 82958 increased P-GluR1, but not P-CREB, in the NAc, and naloxone reduced SKF 82958-mediated P-GluR1 induction specifically in morphine-dependent rats. Together, these results confirm that aversive treatments can increase CREB function in the NAc. Furthermore, they suggest a dependence-associated shift in the molecular mechanisms that regulate the consequences of D 1 receptor stimulation, favoring activation of GluR1 rather than CREB. These data raise the possibility that the rewarding effects of SKF 82958 in morphine-dependent rats involve increased P-GluR1 in the NAc, although the involvement of other brain regions cannot be ruled out. Regardless, these findings suggest for the first time that D 1 agonists might be useful for the treatment of withdrawal symptoms that contribute to the maintenance of opiate addiction in humans.Key words: nucleus accumbens; CREB; GluR1; AMPA; place conditioning; SKF 82958 IntroductionOpiate withdrawal causes somatic abstinence signs as well as a motivational syndrome characterized by dysphoria and depression (Koob and Le Moal, 1997;De Vries and Shippenberg, 2002) in humans. These negative affective states are thought to contribute to addictive behaviors (Koob and Le Moal, 1997;Markou et al., 1998). The nucleus accumbens (NAc), which receives extensive dopaminergic input, plays a key role in opiate reward (Wise, 1989) as well as the motivational and somatic signs of opiate withdrawal (Koob et al., 1992;Harris and Aston-Jones, 1994). The opioid receptor antagonist naloxone precipitates physical withdrawal signs in morphine-dependent rats and produces behaviors, such as conditioned place aversions, that reflect aversive states mediated within the NAc (Stinus et al., 1990).Acute morphine decreases formation of cAMP (Childers, 1991), whereas chronic morphine causes super-sensitivity of cAMP pathways in areas including the NAc (Nestler and Aghajanian, 1997). Precipitated opiate withdrawal unmasks upregulated cAMP pathways, which likely contribute to aversive states. Hypothetically, activation of dopamine (DA) D 1 rece...

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“…There is a substantial amount of literature suggesting that opiates interact with glutamatergic transmission (Gass & Olive, 2008). Most in vitro and in vivo studies have shown that morphine suppresses both basal and evoked increases in extracellular glutamate in NAc and other regions (Sepulveda, Hernandez, Rada, Tucci, & Contreras, 1998). Morphine can also act postsynaptically to suppress glutamate-evoked neuronal excitation (Giacchino & Henriksen, 1998).…”

Section: T a B L Ementioning

confidence: 99%

Quantifying absolute glutamate concentrations in nucleus accumbens of prescription opioid addicts by using ¹H MRS

Liu

et al. 2017

Brain and Behavior

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Introduction The diagnosis of psychoactive substance use disorders has been based primarily on descriptive, symptomatic checklist criteria. In opioid addiction, there are no objective biological indicators specific enough to guide diagnosis, monitor disease status, and evaluate efficacy of therapeutic interventions. Proton magnetic resonance spectroscopy ( 1 H MRS) of the brain has potential to identify and quantify biomarkers for the diagnosis of opioid dependence. The purpose of this study was to detect the absolute glutamate concentration in the nucleus accumbens (NAc) of patients with prescription opioid dependence using 1 H MRS, and to analyze its clinical associations. Methods Twenty patients with clinically diagnosed definitive prescription opioid dependent (mean age = 26.5 ± 4.3 years) and 20 matched healthy controls (mean age = 26.1 ± 3.8 years) participated in this study. Patients were evaluated with the Barratt Impulsiveness Scale (BIS‐11), the Self‐Rating Anxiety Scale (SAS), and the opiate Addiction Severity Inventory (ASI). We used point‐resolved spectroscopy to quantify the absolute concentrations of metabolites (glutamate, choline, N ‐acetylaspartate, glutamine, creatine) within the NAc. The difference between metabolite levels of groups and Pearson's correlation between glutamate levels and psychometric scores in patients were analyzed statistically. Results Glutamate concentrations in the NAc were significantly higher in prescription opiate addicts than in controls ( t = 3.84, p = .001). None of the other metabolites differed significantly between the two groups (all p s > .05). The glutamate concentrations correlated positively with BIS‐11 scores in prescription opiate addicts ( r = .671, p = .001), but not with SAS score and ASI index. Conclusions Glutamate levels in the NAc measured quantitatively with in vivo 1 H MRS could be used as a biomarker to evaluate disease condition in opioid‐dependent patients.

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Effect of Precipitated Withdrawal on Extracellular Glutamate and Aspartate in the Nucleus Accumbens of Chronically Morphine-Treated Rats: An In Vivo Microdialysis Study

Cited by 72 publications

References 28 publications

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Behavioral and Molecular Effects of Dopamine D1 Receptor Stimulation during Naloxone-Precipitated Morphine Withdrawal

Quantifying absolute glutamate concentrations in nucleus accumbens of prescription opioid addicts by using ¹H MRS

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Effect of Precipitated Withdrawal on Extracellular Glutamate and Aspartate in the Nucleus Accumbens of Chronically Morphine-Treated Rats: An In Vivo Microdialysis Study

Cited by 72 publications

References 28 publications

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Behavioral and Molecular Effects of Dopamine D1 Receptor Stimulation during Naloxone-Precipitated Morphine Withdrawal

Quantifying absolute glutamate concentrations in nucleus accumbens of prescription opioid addicts by using 1H MRS

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Quantifying absolute glutamate concentrations in nucleus accumbens of prescription opioid addicts by using ¹H MRS