Ceftriaxone reduces alcohol intake in outbred rats while upregulating xCT in the nucleus accumbens core

Stennett, Bethany; Frankowski, Jan C.; Peris, Joanna; Knackstedt, Lori A.

doi:10.1016/j.pbb.2017.07.001

Cited by 29 publications

(21 citation statements)

References 34 publications

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“…Previous work showed that xCT expression was reduced after scheduled phasic exposure to NIC but not EtOH in the NAc, dorsal striatum, and HIP (Knackstedt et al, 2009, Griffin III et al, 2014, Stennett et al, 2017. Additionally, previously reported studies and our data have not demonstrated any significant reductions in the expression of xCT in the PFC following chronic exposure to NIC (Knackstedt et al, 2009.…”

Section: Accepted Manuscript 17supporting

confidence: 55%

“…Previously, continuous exposure to EtOH for five weeks and phasic exposure to NIC for 21 days reduced GLT-1 expression in the NAc of adult rats (Knackstedt et al, 2009, Alhaddad et al, 2014b, Goodwani et al, 2015. However, others have shown chronic limited access to EtOH did not induce any changes in GLT-1 or xCT expression in adult animals (Griffin et al, 2015, Pati et al, 2016, Stennett et al, 2017. Together these findings indicate that continuous (i.e., notscheduled) exposure to EtOH reduces the expression of GLT-1 in the NAc.…”

Section: Accepted Manuscript 17mentioning

confidence: 67%

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Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats

Alasmari

Bell

Rao

et al. 2018

Pharmacology Biochemistry and Behavior

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Impairment in glutamate neurotransmission mediates the development of dependence upon nicotine (NIC) and ethanol (EtOH). Previous work indicates that continuous access to EtOH or phasic exposure to NIC reduces expression of the glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT) but not the glutamate/aspartate transporter (GLAST). Additionally, metabotropic glutamate receptors (mGluRs) expression was affected following exposure to EtOH or NIC. However, little is known about the effects of EtOH and NIC co-consumption on GLT-1, xCT, GLAST, and mGluR1 expression. In this study, peri-adolescent female alcohol preferring (P) rats were given binge-like access to water, sucrose (SUC), SUC-NIC, EtOH, or EtOH-NIC for four weeks. The present study determined the effects of these reinforcers on GLT-1, xCT, GLAST, and mGluR1 expression in the nucleus accumbens (NAc), hippocampus (HIP) and prefrontal cortex (PFC). GLT-1 and xCT expression were decreased in the NAc following both SUC-NIC and EtOH-NIC. In addition, only xCT expression was downregulated in the HIP in both of these latter groups. Also, glutathione peroxidase (GPx) activity in the HIP was reduced following SUC, SUC-NIC, EtOH, and EtOH-NIC consumption. Similar to previous work, GLAST expression was not altered in any brain region by any of the reinforcers. However, mGluR1 expression was increased in the NAc in the SUC-NIC, EtOH, and EtOH-NIC groups. These results indicate that peri-adolescent binge-like drinking of EtOH or SUC with or without NIC may exert differential effects on astroglial glutamate transporters and receptors. Our data further parallel some of the previous findings observed in adult rats.

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Section: Accepted Manuscript 17supporting

confidence: 55%

Section: Accepted Manuscript 17mentioning

confidence: 67%

Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats

Alasmari

Bell

Rao

et al. 2018

Pharmacology Biochemistry and Behavior

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“…However, such cocaine and ceftriaxone-induced effects identified in rodents may not translate into the clinic, as 50–90% of cocaine users also use alcohol ( Grant and Harford, 1990 ; Rounsaville et al, 1991 ; Anthony et al, 1994 ; Brookoff et al, 1996 ; Kedia et al, 2007 ; Liu et al, 2018 ). Alcohol consumption in outbred Sprague-Dawley rats leads to increased NA core basal glutamate levels during early abstinence, with no changes in GLT-1 and xCT expression, and ceftriaxone is ineffective at changing GLT-1 expression after alcohol ( Pati et al, 2016 ; Stennett et al, 2017 ). Thus, the combination of cocaine and alcohol likely leads to unique NA core glutamate adaptations differing from that of cocaine alone.…”

Section: Introductionmentioning

confidence: 99%

A Rat Model of Cocaine-Alcohol Polysubstance Use Reveals Altered Cocaine Seeking and Glutamate Levels in the Nucleus Accumbens

Stennett

Knackstedt

2020

Front. Neurosci.

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Preclinical models of cocaine use disorder are widely utilized to identify neuroadaptations underlying cocaine seeking and to screen medications to reduce seeking. However, while the majority of cocaine users engage in poly-substance use (PSU), a minority of preclinical studies employ PSU models. We previously reported that when rats consume alcohol after daily intravenous cocaine self-administration, nucleus accumbens (NA) core basal glutamate levels are reduced below those of rats that consumed only cocaine, and do not increase during cue + cocaine-primed reinstatement of cocaine-seeking. Here we used the same model of sequential cocaine and alcohol self-administration to test the hypothesis that a similar pattern of glutamate changes would be observed in the NA core prior to and during a cocaine-primed reinstatement test. Rats underwent intravenous cocaine self-administration followed by access to unsweetened alcohol in the home cage for 12 days. Rats underwent a minimum of 12 daily extinction sessions prior to a cocaine-primed reinstatement test conducted during microdialysis procedures. Contrary to our previous work using the same model, here we found that access to alcohol increased cocaine intake and increased responding during early extinction training. We found that as in our previous work, cocaine + alcohol-consuming rats displayed basal glutamate levels below those of rats that self-administered only cocaine. During the cocaine-primed reinstatement test, rats that consumed only cocaine displayed increased glutamate efflux in the NA core while those that consumed cocaine + alcohol did not. These results indicate that preclinical models of PSU should be utilized to develop experimental therapeutics for the reduction of cocaine seeking.

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“…Furthermore, blockade of EAAT2/GLT-1 was shown to prevent ceftriaxone-mediated decreases in extracellular glutamate in the nucleus accumbens, further implicating EAAT2/GLT-1 induction in the beneficial effects of ceftriaxone on alcohol intake (Das et al, 2015). In contrast, a recent study showed that while ceftriaxone administration during intermittent alcohol access in Sprague Dawley rats did indeed decrease EtOH consumption, this occurred in the absence of EAAT2/ GLT-1 induction in the nucleus accumbens (Stennett et al, 2017). Instead, Stennett et al observed ceftriaxone-mediated induction of another glutamate transporter, the chloridedependent cysteine/glutamate transporter (xCT) encoded by SLC7A11.…”

Section: Excitatory Amino Acid Transporter 2 (Eaat2/glt-1/ Slc1a2)mentioning

confidence: 96%

“…Subsequent studies have largely focused on the therapeutic potential of ceftriaxone. Early on, ceftriaxone was shown to induce the expression of EAAT2/GLT-1 in the prefrontal cortex and nucleus (Abulseoud et al, 2014;Das et al, 2015;Sari et al, 2011Sari et al, , 2016Stennett et al, 2017) Ampicillin (Rao et al, 2015) Cefazolin (Rao et al, 2015) Cefoperazone (Rao et al, 2015) Amoxicillin (Goodwani et al, 2015) Augmentin (Goodwani et al, 2015) Clavulanic Acid (Hakami and Sari, 2017) N-Acetyl Cysteine (Lebourgeois et al, 2018;Quintanilla et al, 2016) N-Acetyl Cysteine (Squeglia et al, 2016; NCT00568087; NCT03018236; NCT03879759; NCT03216954; NCT03707951) Slc6a1 GAT1 GABA Tiagabine (Nguyen et al, 2005;Rimondini et al, 2002;Schmitt et al, 2002) Tiagabine (Myrick et al, 2005;Paparrigopoulos et al, 2010) Slc6a3 DAT Dopamine Modafinil (Maggio et al, 2018) DOV 102,677 (McMillen et al, 2007O'Tousa et al, 2013) Amitifadine (O'Tousa et al, 2013) Modafinil (Joos et al, 2013;NCT00142818;NCT03424681) Slc6a4 SERT Serotonin Fluoxetine (Maurel et al, 1999) Paroxetine (Maurel et al, 1999) Citalopram (Maurel et al, 1999) Fluvoxamine (Lamb and Daws, 2013;Maurel et al, 1999 Fluoxetine (Kranzler et al, 1995;Naranjo et al, 1990) Sertraline (Kranzler et al, 2011) Slc6a9 accumbens of male alcohol-preferring (P) rats, while simultaneously decreasing their voluntary EtOH intake using a 2-bottle choice paradigm (Sari et al, 2011). In the 2-bottle choice paradigm, rats are given access to 2 bot...…”

Section: Excitatory Amino Acid Transporter 2 (Eaat2/glt-1/ Slc1a2)mentioning

confidence: 99%

SLC Neurotransmitter Transporters as Therapeutic Targets for Alcohol Use Disorder: A Narrative Review

McColl

Piquette-Miller

2020

Alcoholism Clin & Exp Res

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Alcohol use disorder (AUD) is 1 of the most prevalent of all substance use disorders and contributes significantly to global disease burden. Despite its prevalence, <10% of individuals with AUD receive treatment. A significant barrier to receiving treatment is a lack of effective pharmacotherapies. While 3 medications have been approved by the FDA for AUD (disulfiram, acamprosate, naltrexone), their efficacy remains low. Furthermore, a number of undesirable side effects associated with these drugs further reduce patient compliance. Thus, research into new effective pharmacotherapies for AUD is warranted. Due to their involvement in regulating synaptic neurotransmitter levels, solute carrier (SLC) transporters could be targeted for developing effective treatment strategies for AUD. Indeed, a number of studies have shown beneficial reductions in alcohol consumption through the use of drugs that target transporters of dopamine, serotonin, glutamate, glycine, and GABA. The purpose of this narrative review is to summarize preclinical and clinical studies from the last 2 decades targeting SLC neurotransmitter transporters for the treatment of AUD. Limitations, as well as future directions for expanding this field, are also discussed.

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Ceftriaxone reduces alcohol intake in outbred rats while upregulating xCT in the nucleus accumbens core

Cited by 29 publications

References 34 publications

Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats

Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats

A Rat Model of Cocaine-Alcohol Polysubstance Use Reveals Altered Cocaine Seeking and Glutamate Levels in the Nucleus Accumbens

SLC Neurotransmitter Transporters as Therapeutic Targets for Alcohol Use Disorder: A Narrative Review

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