Effects of ceftriaxone on ethanol, nicotine or sucrose intake by alcohol-preferring (P) rats and its association with GLT-1 expression

Youssef Sari, Jamie E. Toalston, P. S S Rao, Richard Bell

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Abstract

Increased glutamatergic neurotransmission appears to mediate the reinforcing properties of drugs of abuse, including ethanol (EtOH). We have shown that administration of ceftriaxone (CEF), a β-lactam antibiotic, reduced EtOH intake and increased glutamate transporter 1 (GLT-1) expression in mesocorticolimbic regions of male and female alcohol-preferring (P) rats. In the present study, we tested whether CEF administration would reduce nicotine (NIC) and/or EtOH intake by adult female P rats. P rats were randomly assigned to 4 groups: (a) 5% sucrose (SUC) or 10% SUC [SUC], (b) 5% SUC + 0.07 mg/ml NIC and 10% SUC + 0.14 mg/ml NIC [NIC-SUC], 15% EtOH and 30% EtOH [EtOH] and (d) 15% EtOH + 0.07 mg/ml NIC and 30% EtOH + 0.14 mg/ml NIC [NIC-EtOH]. After achieving stable intakes (4 weeks), the rats were administered 7 consecutive, daily i.p. injections of either saline or 200 mg/kg CEF. The effects of CEF on intake were significant but differed across the reinforcers; such that ml/kg/day SUC was reduced by ~30%, mg/kg/day NIC was reduced by ~70% in the NIC-SUC group and ~40% in the EtOH-NIC group, whereas g/kg/day EtOH was reduced by ~40% in both the EtOH and EtOH-NIC group. The effects of CEF on GLT-1 expression were also studied. We found that CEF significantly increased GLT-1 expression in the prefrontal cortex and the nucleus accumbens of the NIC and NIC-EtOH rats as compared to NIC and NIC-EtOH saline-treated rats. These findings provide further support for GLT-1-associated mechanisms in EtOH and/or NIC abuse. The present results along with previous reports of CEF's efficacy in reducing cocaine self-administration in rats suggest that modulation of GLT-1 expression and/or activity is an important pharmacological target for treating polysubstance abuse and dependence.

Original languageEnglish (US)
Pages (from-to)117-125
Number of pages9
JournalNeuroscience
Volume326
DOIs
StatePublished - Jun 21 2016

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Amino Acid Transport System X-AG
Ceftriaxone
Nicotine
Sucrose
Ethanol
Alcohols
Lactams
Self Administration
Nucleus Accumbens
Street Drugs

Keywords

  • Addiction
  • Alcohol
  • Ceftriaxone
  • Drinking
  • EAAT2
  • Polysubstance

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Effects of ceftriaxone on ethanol, nicotine or sucrose intake by alcohol-preferring (P) rats and its association with GLT-1 expression. / Sari, Youssef; Toalston, Jamie E.; Rao, P. S S; Bell, Richard.

In: Neuroscience, Vol. 326, 21.06.2016, p. 117-125.

Research output: Contribution to journalArticle

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abstract = "Increased glutamatergic neurotransmission appears to mediate the reinforcing properties of drugs of abuse, including ethanol (EtOH). We have shown that administration of ceftriaxone (CEF), a β-lactam antibiotic, reduced EtOH intake and increased glutamate transporter 1 (GLT-1) expression in mesocorticolimbic regions of male and female alcohol-preferring (P) rats. In the present study, we tested whether CEF administration would reduce nicotine (NIC) and/or EtOH intake by adult female P rats. P rats were randomly assigned to 4 groups: (a) 5{\%} sucrose (SUC) or 10{\%} SUC [SUC], (b) 5{\%} SUC + 0.07 mg/ml NIC and 10{\%} SUC + 0.14 mg/ml NIC [NIC-SUC], 15{\%} EtOH and 30{\%} EtOH [EtOH] and (d) 15{\%} EtOH + 0.07 mg/ml NIC and 30{\%} EtOH + 0.14 mg/ml NIC [NIC-EtOH]. After achieving stable intakes (4 weeks), the rats were administered 7 consecutive, daily i.p. injections of either saline or 200 mg/kg CEF. The effects of CEF on intake were significant but differed across the reinforcers; such that ml/kg/day SUC was reduced by ~30{\%}, mg/kg/day NIC was reduced by ~70{\%} in the NIC-SUC group and ~40{\%} in the EtOH-NIC group, whereas g/kg/day EtOH was reduced by ~40{\%} in both the EtOH and EtOH-NIC group. The effects of CEF on GLT-1 expression were also studied. We found that CEF significantly increased GLT-1 expression in the prefrontal cortex and the nucleus accumbens of the NIC and NIC-EtOH rats as compared to NIC and NIC-EtOH saline-treated rats. These findings provide further support for GLT-1-associated mechanisms in EtOH and/or NIC abuse. The present results along with previous reports of CEF's efficacy in reducing cocaine self-administration in rats suggest that modulation of GLT-1 expression and/or activity is an important pharmacological target for treating polysubstance abuse and dependence.",
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AU - Bell, Richard

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N2 - Increased glutamatergic neurotransmission appears to mediate the reinforcing properties of drugs of abuse, including ethanol (EtOH). We have shown that administration of ceftriaxone (CEF), a β-lactam antibiotic, reduced EtOH intake and increased glutamate transporter 1 (GLT-1) expression in mesocorticolimbic regions of male and female alcohol-preferring (P) rats. In the present study, we tested whether CEF administration would reduce nicotine (NIC) and/or EtOH intake by adult female P rats. P rats were randomly assigned to 4 groups: (a) 5% sucrose (SUC) or 10% SUC [SUC], (b) 5% SUC + 0.07 mg/ml NIC and 10% SUC + 0.14 mg/ml NIC [NIC-SUC], 15% EtOH and 30% EtOH [EtOH] and (d) 15% EtOH + 0.07 mg/ml NIC and 30% EtOH + 0.14 mg/ml NIC [NIC-EtOH]. After achieving stable intakes (4 weeks), the rats were administered 7 consecutive, daily i.p. injections of either saline or 200 mg/kg CEF. The effects of CEF on intake were significant but differed across the reinforcers; such that ml/kg/day SUC was reduced by ~30%, mg/kg/day NIC was reduced by ~70% in the NIC-SUC group and ~40% in the EtOH-NIC group, whereas g/kg/day EtOH was reduced by ~40% in both the EtOH and EtOH-NIC group. The effects of CEF on GLT-1 expression were also studied. We found that CEF significantly increased GLT-1 expression in the prefrontal cortex and the nucleus accumbens of the NIC and NIC-EtOH rats as compared to NIC and NIC-EtOH saline-treated rats. These findings provide further support for GLT-1-associated mechanisms in EtOH and/or NIC abuse. The present results along with previous reports of CEF's efficacy in reducing cocaine self-administration in rats suggest that modulation of GLT-1 expression and/or activity is an important pharmacological target for treating polysubstance abuse and dependence.

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