A microdialysis study of extracellular levels of acamprosate and naltrexone in the rat brain following acute and repeated administration

Costanza Burattini, Andrew J. McGeehan, William C. Griffin, Justin T. Gass, Jennifer R. Kinder, Patricia H. Janak, M. Foster Olive

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Acamprosate and naltrexone are widely used in the treatment of alcoholism. However, numerous studies in rodents have shown differential effects of these compounds on alcohol consumption and/or relapse-like behavior following acute versus repeated administration. In order to determine if these differential behavioral effects could be attributable to changes in extracellular levels of these compounds, we used in vivo microdialysis to monitor extracellular levels of acamprosate and naltrexone in the rat medial prefrontal cortex following acute and repeated intraperitoneal administration. For acute treatment, animals received a single administration of acamprosate (100 or 300 mg/kg) or naltrexone (1 or 3 mg/kg). For repeated treatment, animals received once daily treatment with saline, acamprosate (300 mg/kg) or naltrexone (3 mg/kg) for 10 days before a subsequent challenge with the compound according to their respective pretreatment group. Dialysate levels of acamprosate and naltrexone were analyzed by liquid chromatography-tandem mass spectrometry and high performance liquid chromatography, respectively. Following acute administration, peak dialysate concentrations of each compound were dose-dependent, observed within 1 hour of administration, and were found to be in the low micromolar range for acamprosate and in the low to mid-nanomolar range for naltrexone. Pretreatment with acamprosate, but not naltrexone, for 10 days resulted in higher dialysate concentrations of the compound relative to saline-pretreated controls. Thus, repeated administration of acamprosate, but not naltrexone, results in augmented extracellular levels of the compound in the brain relative to saline-pretreated controls, which may explain the need for repeated administration of acamprosate in order to observe effects on alcohol consumption and/or relapse.

Original languageEnglish (US)
Pages (from-to)70-79
Number of pages10
JournalAddiction Biology
Volume13
Issue number1
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Keywords

  • Acamprosate
  • Extracellular fluid
  • Microdialysis
  • Naltrexone
  • Prefrontal cortex
  • Rat

ASJC Scopus subject areas

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

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