Effects of Ceftriaxone on Glial Glutamate Transporters in Wistar Rats Administered Sequential Ethanol and Methamphetamine

Althobaiti, Yusuf S.; Alshehri, Fahad S.; Almalki, Atiah H.; Sari, Youssef

doi:10.3389/fnins.2016.00427

Cited by 28 publications

(21 citation statements)

References 94 publications

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“…Likewise, no change in GLT-1 in midbrain, NAc, dorsal striatum, or PFC is reported following amphetamine sensitization ( Sidiropoulou et al, 2001 ). Repeated high doses of methamphetamine (10 mg/kg x 4, every 2 hours) decrease GLT-1 in striatum and hippocampus ( Althobaiti et al, 2016 ). The disparity between these results likely reflects differences in dosing and treatment regimens.…”

Section: Eaat2/glt-1mentioning

confidence: 99%

“…Ceftriaxone reduces drug-induced reinstatement of methamphetamine and nicotine CPP ( Abulseoud, 2012 ) ( Alajaji et al, 2013 ). Likewise, ceftriaxone reduces physical, somatic, and affective nicotine withdrawal signs in ICR mice ( Alajaji et al, 2013 ) and nicotine intake in female P rats ( Sari et al, 2016 ). Subthreshold doses of MK-801, an NMDAR antagonist, plus ceftriaxone reduce the acquisition of morphine CPP and block extinction and reinstatement of preference ( Fan et al, 2012 ).…”

Section: Translational Studies On Eaat Pharmacotherapies For Addictiomentioning

confidence: 99%

“…Therapeutic doses of ceftriaxone alone given during extinction block reinstatement of morphine CPP and normalize plasticity in NAc shell medium spiny neurons ( Hearing et al, 2016 ). Repeated ceftriaxone treatment reduces alcohol drinking in male and female P rats coincident with an increase in GLT-1 levels in PFC and NAc ( Sari et al, 2011 , 2016 ). Other beta-lactams, ampicillin, cefazolin, cefoperazone, and amoxicillin, decrease ethanol intake and increase GLT-1 expression in PFC and NAc ( Rao et al, 2015b ; Hakami et al, 2016 ).…”

Section: Translational Studies On Eaat Pharmacotherapies For Addictiomentioning

confidence: 99%

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Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse

Spencer

Kalivas

2017

International Journal of Neuropsychopharmacology

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Drug addiction has often been described as a “hijacking” of the brain circuits involved in learning and memory. Glutamate is the principal excitatory neurotransmitter in the brain, and its contribution to synaptic plasticity and learning processes is well established in animal models. Likewise, over the past 20 years the addiction field has ascribed a critical role for glutamatergic transmission in the development of addiction. Chronic drug use produces enduring neuroadaptations in corticostriatal projections that are believed to contribute to a maladaptive deficit in inhibitory control over behavior. Much of this research focuses on the role played by ionotropic glutamate receptors directly involved in long-term potentiation and depression or metabotropic receptors indirectly modulating synaptic plasticity. Importantly, the balance between glutamate release and clearance tightly regulates the patterned activation of these glutamate receptors, emphasizing an important role for glutamate transporters in maintaining extracellular glutamate levels. Five excitatory amino acid transporters participate in active glutamate reuptake. Recent evidence suggests that these glutamate transporters can be modulated by chronic drug use at a variety of levels. In this review, we synopsize the evidence and mechanisms associated with drug-induced dysregulation of glutamate transport. We then summarize the preclinical and clinical data suggesting that glutamate transporters offer an effective target for the treatment of drug addiction. In particular, we focus on the role that altered glutamate transporters have in causing drug cues and contexts to develop an intrusive quality that guides maladaptive drug seeking behaviors.

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Section: Eaat2/glt-1mentioning

confidence: 99%

Section: Translational Studies On Eaat Pharmacotherapies For Addictiomentioning

confidence: 99%

Section: Translational Studies On Eaat Pharmacotherapies For Addictiomentioning

confidence: 99%

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Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse

Spencer

Kalivas

2017

International Journal of Neuropsychopharmacology

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“…In addition, chronic ethanol drinking was shown to decrease GLT-1 and xCT expression in the NAc (Alhaddad et al, 2014; Das et al, 2015b). Therefore, CEF treatment decreased ethanol intake and upregulated GLT-1 in the NAc and PFC (Alhaddad et al, 2014; Althobaiti et al, 2016b; Sari et al, 2011; Sari et al, 2013). CEF’s upregulatory effect on GLT-1 expression is suggested to be mainly attributed to the β-lactam ring found in this drug and other β-lactam antibiotics (Rothstein et al, 2005).…”

Section: Introductionmentioning

confidence: 98%

Effects of Clavulanic Acid Treatment on Reinstatement to Methamphetamine, Glial Glutamate Transporters, and mGluR 2/3 Expression in P Rats Exposed to Ethanol

et al. 2018

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Evidence demonstrated that glutamatergic system is implicated in mediating relapse to several drugs of abuse, including methamphetamine (METH). Glutamate homeostasis is maintained by a number of glutamate transporters, such as glutamate transporter type 1 (GLT-1), cystine/glutamate transporter (xCT), and glutamate aspartate transporter (GLAST). In addition, group II metabotropic glutamate receptors (mGluR2/3) were found to be implicated in relapse-seeking behavior. Ample evidence showed that β-lactam antibiotics are effective in upregulating GLT-1 and xCT expression, thus improving glutamate homeostasis and attenuating relapse to drugs of abuse. In this study, we investigated the reinstatement of METH using conditioned place preference (CPP) in male alcohol-preferring (P) rats exposed to home-cage free choice ethanol drinking. Here, we tested the effect of clavulanic acid (CA), a β-lactam, on the reinstatement of METH-seeking and ethanol drinking. In addition, we examined the expression of GLT-1, xCT and GLAST as well as metabotropic glutamate receptor (mGluR2/3) in the nucleus accumbens (NAc) shell, NAc core and dorsomedial prefrontal cortex (dmPFC). A priming i.p. injection of METH reinstated preference in METH-paired chamber following extinction. Chronic exposure to ethanol decreased the expression of GLT-1 and xCT in the NAc shell, but not in the NAc core or dmPFC. CA treatment blocked the reinstatement of METH-seeking, decreased ethanol intake and restored the expression of GLT-1 and xCT in the NAc shell. In addition, the expression of mGluR2/3 was increased by CA treatment in the NAc shell and dmPFC. These findings suggest that these glutamate transporters and mGluR2/3 might be potential therapeutic targets for the attenuation of reinstatement to METH-seeking.

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“…Studies from ours and others have reported that GLT-1 was downregulated in the NAc following exposure to several drugs of abuse, including ethanol and cocaine (Ginsberg et al, 1995, Danbolt, 2001, Knackstedt et al, 2009, Sari and Sreemantula, 2012, Fischer et al, 2013, Shen et al, 2014). Importantly, a study from our laboratory showed that sequential exposure to ethanol and repeated high dose methamphetamine caused additive downregulation of GLT-1 in the NAc than either drug exposed alone (Althobaiti et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Effects of repeated cocaine exposure and withdrawal on voluntary ethanol drinking, and the expression of glial glutamate transporters in mesocorticolimbic system of P rats

Hammad

Althobaiti

Das

et al. 2017

Molecular and Cellular Neuroscience

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Glutamatergic neurotransmission within the brain’s reward circuits plays a major role in the reinforcing properties of both ethanol and cocaine. Glutamate homeostasis is regulated by several glutamate transporters, including glutamate transporter type 1 (GLT-1), cystine/glutamate transporter (xCT), and glutamate aspartate transporter (GLAST). Cocaine exposure has been shown to induce a dysregulation in glutamate homeostasis and a decrease in the expression of GLT-1 and xCT in the nucleus accumbens (NAc). In this study, alcohol preferring (P) rats were exposed to free-choice of ethanol (15% and 30%) and/ or water for five weeks. On Week 6, rats were administered (i.p.) cocaine (10 and 20 mg/kg) or saline for 12 consecutive days. This study tested two groups of rats: the first group was euthanized after seven days of repeated cocaine i.p. injection, and the second group was deprived from cocaine for five days and euthanized at Day 5 after cocaine withdrawal. Only repeated cocaine (20 mg/kg, i.p.) exposure decreased ethanol intake from Day 3 through Day 8. Co-exposure of cocaine and ethanol decreased the relative mRNA expression and the expression of GLT-1 in the NAc but not in the medial prefrontal cortex (mPFC). Importantly, co-exposure of cocaine and ethanol decreased relative expression of xCT in the NAc but not in the mPFC. Our findings demonstrated that chronic cocaine exposure affects ethanol intake; and ethanol and cocaine co-abuse alters the expression of glial glutamate transporters.

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Effects of Ceftriaxone on Glial Glutamate Transporters in Wistar Rats Administered Sequential Ethanol and Methamphetamine

Cited by 28 publications

References 94 publications

Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse

Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse

Effects of Clavulanic Acid Treatment on Reinstatement to Methamphetamine, Glial Glutamate Transporters, and mGluR 2/3 Expression in P Rats Exposed to Ethanol

Effects of repeated cocaine exposure and withdrawal on voluntary ethanol drinking, and the expression of glial glutamate transporters in mesocorticolimbic system of P rats

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