Dynamic interactions of ceftriaxone and environmental variables suppress amphetamine seeking

Garcia, Erik J.; Arndt, David L.; Cain, Mary E.

doi:10.1016/j.brainres.2019.01.044

Cited by 12 publications

(11 citation statements)

References 57 publications

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“…We replicate prior work in that EC rats self-administer less low-unit dose amphetamine but did not differ from IC and SC rats for moderate or high doses (Arndt et al, 2015;Bardo et al, 2001;Garcia, Arndt, & Cain, 2019;Green et al, 2002). In addition, we replicate prior work that shows EC rats respond less than IC and SC rats during extinction (Alvers, Marusich, Gipson, Beckmann, & Bardo, 2012;Green et al, 2010;Stairs, Klein, & Bardo, 2006).…”

Section: Discussionsupporting

confidence: 77%

Histone deacetylase inhibition differentially attenuates cue-induced reinstatement: An interaction of environment and acH3K9 expression in the dorsal striatum.

Arndt¹,

Wukitsch²,

Garcia³

et al. 2019

Behavioral Neuroscience

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Substance use disorder is driven by complex gene-environment interactions. Epigenetic histone regulation is a significant contributor to several behavioral phenotypes of drug abuse. The primary epigenetic mechanisms that drive drug taking and drug seeking are still being investigated, and it is unclear how environmental conditions alter epigenetic histone acetylation to change behaviors geared toward drug reward. This study examined the effects of environmental condition on amphetamine self-administration, and whether drug-taking and drug-seeking behaviors could be influenced through inhibition of an epigenetic regulator, histone deacetylase (HDAC). Male rats reared for 30 days in enriched (EC), isolated (IC), or standard conditions (SC) prior to amphetamine (0.03, 0.05, 0.1 mg/kg/infusion, IV) self-administration, extinction, and reinstatement sessions. The HDAC inhibitor, Trichostatin A (TsA; 0.3 mg/kg, IV), was injected 30 min prior to operant sessions. After amphetamine-induced reinstatement (0.25 mg/kg, subcutaneous [s.c.]), tissue was extracted for Western blot analyses of acetylated histone H3 lysine 9 (acH3K9) in the nucleus accumbens (NAc) and dorsal striatum (DSt). While TsA did not significantly affect amphetamine self-administration or extinction, TsA decreased cue-, but not drug-induced reinstatement in IC rats only. In the DSt, but not in the NAc, IC rats exhibited significantly less acH3K9 expression than EC and SC rats, irrespective of TsA treatment. HDAC inhibition decreases cue-induced reinstatement of amphetamine seeking in IC rats. While IC rats exhibit less acH3K9 expression in the DSt, future studies are needed to elucidate the critical epigenetic factors that drive substance abuse, particularly in vulnerable populations.

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Section: Discussionsupporting

confidence: 77%

Histone deacetylase inhibition differentially attenuates cue-induced reinstatement: An interaction of environment and acH3K9 expression in the dorsal striatum.

Arndt¹,

Wukitsch²,

Garcia³

et al. 2019

Behavioral Neuroscience

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“…Since then, ceftriaxone has been the most commonly used β-lactam to increase GLT-1 levels, which was subsequently found to also promote the expression of xCT and increase system Xc − activity [155]. Ceftriaxone has been shown to reduce the reinstatement of drug paired behavior and seeking of cocaine [156], amphetamine [157], ethanol (including direct inhibition of consumption) [158][159][160], opioids [161], and nicotine [162], showing the broad-spectrum of the recovering of glutamate homeostasis in the treatment of drug addiction. Methamphetamine self-administration also reduced extracellular glutamate levels in the NAcc and prefrontal cortex of rats after an extinction period [149].…”

Section: The Recovery Of Glt-1 and System XC − Activities Inhibits Drmentioning

confidence: 99%

Oxidative Stress and Neuroinflammation as a Pivot in Drug Abuse. A Focus on the Therapeutic Potential of Antioxidant and Anti-Inflammatory Agents and Biomolecules

et al. 2020

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Drug abuse is a major global health and economic problem. However, there are no pharmacological treatments to effectively reduce the compulsive use of most drugs of abuse. Despite exerting different mechanisms of action, all drugs of abuse promote the activation of the brain reward system, with lasting neurobiological consequences that potentiate subsequent consumption. Recent evidence shows that the brain displays marked oxidative stress and neuroinflammation following chronic drug consumption. Brain oxidative stress and neuroinflammation disrupt glutamate homeostasis by impairing synaptic and extra-synaptic glutamate transport, reducing GLT-1, and system Xc− activities respectively, which increases glutamatergic neurotransmission. This effect consolidates the relapse-promoting effect of drug-related cues, thus sustaining drug craving and subsequent drug consumption. Recently, promising results as experimental treatments to reduce drug consumption and relapse have been shown by (i) antioxidant and anti-inflammatory synthetic molecules whose effects reach the brain; (ii) natural biomolecules secreted by mesenchymal stem cells that excel in antioxidant and anti-inflammatory properties, delivered via non-invasive intranasal administration to animal models of drug abuse and (iii) potent anti-inflammatory microRNAs and anti-miRNAs which target the microglia and reduce neuroinflammation and drug craving. In this review, we address the neurobiological consequences of brain oxidative stress and neuroinflammation that follow the chronic consumption of most drugs of abuse, and the current and potential therapeutic effects of antioxidants and anti-inflammatory agents and biomolecules to reduce these drug-induced alterations and to prevent relapse.

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“…Lever press training, AMP self‐administration and AMP‐seeking tests were conducted in standard operant conditioning chambers (ENV‐001, Med Associates, St. Albans, VT, USA) enclosed in a sound‐attenuating and ventilated cubicle. AMP or SAL infusions were administered via a syringe pump (PHM‐100, Med Associates) connected to a 10‐ml syringe (Arndt, Garcia, et al, 2015;Arndt, Johns, et al, 2015; Garcia et al, 2019; Garcia & Cain, 2020).…”

Section: Methodsmentioning

confidence: 99%

“…At PND 52 rats were food restricted to 85% to facilitate lever press training (~3 days) (Arndt et al, 2019; Garcia et al, 2019). During a 30‐min lever press training session, a single active lever press (FR‐1) delivered a 20% sucrose solution in a recessed food receptacle.…”

Section: Methodsmentioning

confidence: 99%

Isolation housing elevates amphetamine seeking independent of nucleus accumbens glutamate receptor adaptations

Garcia

Cain

2021

Eur J of Neuroscience

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Overdose death rates caused by psychostimulants have increased by 22.3% annually from 2008 to 2017. Cue-evoked drug craving progressively increases and contributes to perpetual relapse. Preclinical models have determined that glutamate receptor plasticity within the nucleus accumbens (NAc) drives amplified cue-evoked drug seeking after prolonged abstinence (>40 days).Isolated condition (IC) rearing increases cocaine and amphetamine (AMP) self-administration and cue-induced reinstatement. We tested the hypothesis that housing in the IC will augment AMP seeking after short and prolonged abstinence from AMP self-administration when compared with rats reared in the enrichment condition (EC). EC and IC male rats acquired stable AMP or SAL self-administration and were tested in a cue-induced AMP-seeking test after 1 and 40 days of abstinence. After the seeking test, the whole NAc was extracted and prepared for western blot analysis. Results indicate that IC rats had more active lever presses during a brief extinction interval and during the cue-induced seeking test. After 40 days of abstinence, IC rats had more active lever presses than EC rats during the cue-induced seeking test. Western blots indicated that the expression ratio between GluA1:mGlur5 was reduced only in IC-AMP-trained rats and the ratio between GluA1:mGlur1 was positively correlated with AMP seeking after prolonged abstinence in IC-AMP rats.These results indicate that IC housing engenders a vulnerable phenotype prone to persistent AMP seeking. The behavioural momentum of this vulnerable phenotype is further revealed when AMP-associated cues are presented following prolonged abstinence.

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Dynamic interactions of ceftriaxone and environmental variables suppress amphetamine seeking

Cited by 12 publications

References 57 publications

Histone deacetylase inhibition differentially attenuates cue-induced reinstatement: An interaction of environment and acH3K9 expression in the dorsal striatum.

Histone deacetylase inhibition differentially attenuates cue-induced reinstatement: An interaction of environment and acH3K9 expression in the dorsal striatum.

Oxidative Stress and Neuroinflammation as a Pivot in Drug Abuse. A Focus on the Therapeutic Potential of Antioxidant and Anti-Inflammatory Agents and Biomolecules

Isolation housing elevates amphetamine seeking independent of nucleus accumbens glutamate receptor adaptations

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