Ceftriaxone, a beta-lactam antibiotic, reduces ethanol consumption in alcohol-preferring rats

Youssef Sari, Makiko Sakai, Jason M. Weedman, George V. Rebec, Richard Bell

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Aims: Changes in glutamatergic transmission affect many aspects of neuroplasticity associated with ethanol and drug addiction. For instance, ethanol- and drug-seeking behavior is promoted by increased glutamate transmission in key regions of the motive circuit. We hypothesized that because glutamate transporter 1 (GLT1) is responsible for the removal of most extracellular glutamate, up-regulation or activation of GLT1 would attenuate ethanol consumption. Methods: Alcohol-preferring (P) rats were given 24 h/day concurrent access to 15 and 30% ethanol, water and food for 7 weeks. During Week 6, P rats received either 25, 50, 100 or 200 mg/kg ceftriaxone (CEF, i.p.), a β-lactam antibiotic known to elevate GLT1 expression, or a saline vehicle for five consecutive days. Water intake, ethanol consumption and body weight were measured daily for 15 days starting on Day 1 of injections. We also tested the effects of CEF (100 and 200 mg/kg, i.p.) on daily sucrose (10%) consumption as a control for motivated behavioral drinking. Results: Statistical analyses revealed a significant reduction in daily ethanol, but not sucrose, consumption following CEF treatment. During the post treatment period, there was a recovery of ethanol intake across days. Dose-dependent increases in water intake were manifest concurrent with the CEF-induced decreases in ethanol intake. Nevertheless, CEF did not affect body weight. An examination of a subset of the CEF-treated ethanol-drinking rats, on the third day post CEF treatment, revealed increases in GTL1 expression levels within the prefrontal cortex and nucleus accumbens. Conclusions: These results indicate that CEF effectively reduces ethanol intake, possibly through activation of GLT1, and may be a potential therapeutic drug for alcohol addiction treatment.

Original languageEnglish
Article numberagr023
Pages (from-to)239-246
Number of pages8
JournalAlcohol and Alcoholism
Volume46
Issue number3
DOIs
StatePublished - May 2011

Fingerprint

Ceftriaxone
beta-Lactams
Alcohol Drinking
Rats
Ethanol
Alcohols
Anti-Bacterial Agents
Amino Acid Transport System X-AG
Drinking
Substance-Related Disorders
Sucrose
Water
Glutamic Acid
Chemical activation
Body Weight
Drug-Seeking Behavior
Pharmaceutical Preparations
Therapeutics
Lactams
Neuronal Plasticity

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

Cite this

Ceftriaxone, a beta-lactam antibiotic, reduces ethanol consumption in alcohol-preferring rats. / Sari, Youssef; Sakai, Makiko; Weedman, Jason M.; Rebec, George V.; Bell, Richard.

In: Alcohol and Alcoholism, Vol. 46, No. 3, agr023, 05.2011, p. 239-246.

Research output: Contribution to journalArticle

Sari, Youssef ; Sakai, Makiko ; Weedman, Jason M. ; Rebec, George V. ; Bell, Richard. / Ceftriaxone, a beta-lactam antibiotic, reduces ethanol consumption in alcohol-preferring rats. In: Alcohol and Alcoholism. 2011 ; Vol. 46, No. 3. pp. 239-246.
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abstract = "Aims: Changes in glutamatergic transmission affect many aspects of neuroplasticity associated with ethanol and drug addiction. For instance, ethanol- and drug-seeking behavior is promoted by increased glutamate transmission in key regions of the motive circuit. We hypothesized that because glutamate transporter 1 (GLT1) is responsible for the removal of most extracellular glutamate, up-regulation or activation of GLT1 would attenuate ethanol consumption. Methods: Alcohol-preferring (P) rats were given 24 h/day concurrent access to 15 and 30{\%} ethanol, water and food for 7 weeks. During Week 6, P rats received either 25, 50, 100 or 200 mg/kg ceftriaxone (CEF, i.p.), a β-lactam antibiotic known to elevate GLT1 expression, or a saline vehicle for five consecutive days. Water intake, ethanol consumption and body weight were measured daily for 15 days starting on Day 1 of injections. We also tested the effects of CEF (100 and 200 mg/kg, i.p.) on daily sucrose (10{\%}) consumption as a control for motivated behavioral drinking. Results: Statistical analyses revealed a significant reduction in daily ethanol, but not sucrose, consumption following CEF treatment. During the post treatment period, there was a recovery of ethanol intake across days. Dose-dependent increases in water intake were manifest concurrent with the CEF-induced decreases in ethanol intake. Nevertheless, CEF did not affect body weight. An examination of a subset of the CEF-treated ethanol-drinking rats, on the third day post CEF treatment, revealed increases in GTL1 expression levels within the prefrontal cortex and nucleus accumbens. Conclusions: These results indicate that CEF effectively reduces ethanol intake, possibly through activation of GLT1, and may be a potential therapeutic drug for alcohol addiction treatment.",
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