Effects of ceftriaxone on conditioned nicotine reward in rats

Philogene-Khalid, Helene L.; Simmons, Steven J.; Muschamp, John W.

doi:10.1097/fbp.0000000000000314

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…The glial GLT-1 modulator, ceftriaxone, has been the most extensively studied in pre-clinical models. Ceftriaxone has been shown to reduce acquisition and reinstatement of nicotine CPP, nicotine intake and withdrawal [351][352][353]. NAC has shown similar effects.…”

Section: Pre-clinical Studiesmentioning

confidence: 96%

Potential of Glial Cell Modulators in the Management of Substance Use Disorders

Jones

2020

CNS Drugs

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The pervasive and devastating nature of substance use disorders underlies the need for the continued development of novel pharmacotherapies. We now know that glia play a much greater role in neuronal processes than once believed. The various types of glial cells (e.g., astrocytes, microglial, oligodendrocytes) participate in various functions that are crucial to healthy central nervous system function. Drugs of abuse have been shown to interact with glia in ways that directly contribute to the pharmacodynamic effects responsible for their abuse potential. Through their effect upon glia, drugs of abuse also alter brain function resulting in behavioral changes associated with substance use disorders. Therefore, drug-induced changes in glia and neuroinflammatory processes have been investigated to treat various aspects of drug abuse and dependence. This manuscript presents a brief overview of the effects of each of the major classes of addictive drugs on glia. Next, the paper reviews the pre-clinical and clinical studies assessing the effects that glial modulators have on abuse-related behavioral effects, such as pleasure, withdrawal, and motivation. There is a strong body of pre-clinical literature demonstrating the general effectiveness of several glia-modulating drugs in models of reward and relapse. Clinical studies have also yielded promising results, though not as robust. There is still much to disentangle regarding the integration between addictive drugs and glial cells. Improved understanding of the relationship between glia and the pathophysiology of drug abuse should allow for more precise exploration in the development and testing of glial-directed treatments for substance use disorders. The Need for Continued Discovery of Medications to Treat Substance Use DisordersDrug abuse is a chronic, relapsing disease characterized by dysfunction in brain reward-, motivation-, and memory-related circuitry [1]. Compulsive drug seeking and use, despite harmful consequences, results in progressive disability and can lead to premature mortality

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Section: Pre-clinical Studiesmentioning

confidence: 96%

Potential of Glial Cell Modulators in the Management of Substance Use Disorders

Jones

2020

CNS Drugs

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“…Drugs of abuse are also known to alter Glu homeostasis in areas involved in reward processing, particularly with chronic administration, and chiefly via downregulation of GLT‐1 (Fischer et al, 2013; Fischer‐Smith et al, 2012; Saeedi et al, 2021). Here again, CEF has been shown to be effective in restoring GLT‐1 mediated transport capacity and attenuate drug seeking behavior (Agostini et al, 2020; Bechard & Knackstedt, 2019; Bechard et al, 2021; Philogene‐Khalid et al, 2017; Rasmussen et al, 2011; Shen et al, 2014).…”

Section: Mblac1: Swip‐10 Ortholog and Target For Neuroprotective Anti...mentioning

confidence: 99%

Sink or swim: Does a worm paralysis phenotype hold clues to neurodegenerative disease?

Rodriguez,

Blakely

2023

Journal Cellular Physiology

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Receiving a neurodegenerative disease (NDD) diagnosis, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, or amyotrophic lateral sclerosis, is devastating, particularly given the limited options for treatment. Advances in genetic technologies have allowed for efficient modeling of NDDs in animals and brought hope for new disease‐modifying medications. The complexity of the mammalian brain and the costs and time needed to identify and develop therapeutic leads limits progress. Modeling NDDs in invertebrates, such as the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, offers orders of magnitude increases in speed of genetic analysis and manipulation, and can be pursued at substantially reduced cost, providing an important, platform complement and inform research with mammalian NDD models. In this review, we describe how our efforts to exploit C. elegans for the study of neural signaling and health led to the discovery of a paralytic phenotype (swimming‐induced paralysis) associated with altered dopamine signaling and, surprisingly, to the discovery of a novel gene and pathway whose dysfunction in glial cells triggers neurodegeneration. Research to date on swip‐10 and its putative mammalian ortholog MBLAC1, suggests that a tandem analysis will offer insights into NDD mechanisms and insights into novel, disease‐modifying therapeutics.

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“…CEF treatment (200 mg/kg/day) twice daily for 4 days reduced reinstatement to nicotine in mice using the CPP paradigm ( Alajaji et al, 2013 ). We have shown that short-term nicotine abstinence is associated with reduced glutamate concentration in the dACC in humans ( Abulseoud et al, 2020 ), and that CEF decreased nicotine withdrawal manifestations in rats ( Alajaji et al, 2013 ) and attenuated nicotine preference using the CPP paradigm ( Philogene-Khalid et al, 2017 ). To the best of our knowledge, there are only few studies that report the efficacy of CEF pretreatment in reducing nicotine-seeking behavior, preference in CPP, and withdrawal manifestations.…”

Section: Regulation Of Hyperglutamatergic State With Ceftriaxonementioning

confidence: 99%

Ceftriaxone as a Novel Therapeutic Agent for Hyperglutamatergic States: Bridging the Gap Between Preclinical Results and Clinical Translation

Abulseoud

Alasmari²,

Hussein³

et al. 2022

Front. Neurosci.

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Dysregulation of glutamate homeostasis is a well-established core feature of neuropsychiatric disorders. Extracellular glutamate concentration is regulated by glutamate transporter 1 (GLT-1). The discovery of a beta-lactam antibiotic, ceftriaxone (CEF), as a safe compound with unique ability to upregulate GLT-1 sparked the interest in testing its efficacy as a novel therapeutic agent in animal models of neuropsychiatric disorders with hyperglutamatergic states. Indeed, more than 100 preclinical studies have shown the efficacy of CEF in attenuating the behavioral manifestations of various hyperglutamatergic brain disorders such as ischemic stroke, amyotrophic lateral sclerosis (ALS), seizure, Huntington’s disease, and various aspects of drug use disorders. However, despite rich and promising preclinical data, only one large-scale clinical trial testing the efficacy of CEF in patients with ALS is reported. Unfortunately, in that study, there was no significant difference in survival between placebo- and CEF-treated patients. In this review, we discussed the translational potential of preclinical efficacy of CEF based on four different parameters: (1) initiation of CEF treatment in relation to induction of the hyperglutamatergic state, (2) onset of response in preclinical models in relation to onset of GLT-1 upregulation, (3) mechanisms of action of CEF on GLT-1 expression and function, and (4) non-GLT-1-mediated mechanisms for CEF. Our detailed review of the literature brings new insights into underlying molecular mechanisms correlating the preclinical efficacy of CEF. We concluded here that CEF may be clinically effective in selected cases in acute and transient hyperglutamatergic states such as early drug withdrawal conditions.

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Effects of ceftriaxone on conditioned nicotine reward in rats

Cited by 8 publications

References 23 publications

Potential of Glial Cell Modulators in the Management of Substance Use Disorders

Potential of Glial Cell Modulators in the Management of Substance Use Disorders

Sink or swim: Does a worm paralysis phenotype hold clues to neurodegenerative disease?

Ceftriaxone as a Novel Therapeutic Agent for Hyperglutamatergic States: Bridging the Gap Between Preclinical Results and Clinical Translation

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