Attenuation of reinstatement of methamphetamine-, sucrose-, and food-seeking behavior in rats by fenobam, a metabotropic glutamate receptor 5 negative allosteric modulator

Lucas R. Watterson, Peter R. Kufahl, Natali E. Nemirovsky, Kaveish Sewalia, Lauren E. Hood, Michael Olive

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Rationale: Methamphetamine (METH) is a highly potent and addictive psychostimulant with severe detrimental effects to the health of users. Currently, METH addiction is treated with a combination of cognitive and behavioral therapies, but these traditional approaches suffer from high relapse rates. Furthermore, there are currently no pharmacological treatment interventions approved by the FDA specifically for the treatment of METH addiction. Objectives: Metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulators (NAMs) have shown promise in significantly attenuating drug self-administration and drug-seeking in reinstatement paradigms. However, studies assessing the potential efficacy of mGluR5 NAMs that have been tested in human subjects are lacking. The current study sought to assess the effect of the mGluR5 NAM fenobam on METH-seeking behavior. Methods: Rats were trained to self-administer METH (0.05 mg/kg i.v.), and following extinction, tested for effects of fenobam (5, 10, or 15 mg/kg intraperitoneal) on cue- and drug-induced reinstatement of METH-seeking. To determine if fenobam also alters reinstatement of seeking of natural reinforcers, separate groups of rats were trained to self-administer sucrose or food pellets and were tested for the effects of fenobam on cue-induced reinstatement of sucrose- and food-seeking. Results: Fenobam attenuated drug- and cue-induced reinstatement of METH-seeking behavior at doses of 10 and 15 mg/kg. Fenobam also attenuated cue-induced reinstatement of sucrose- and food-seeking at all doses tested. Conclusions: The mGluR5 NAM fenobam attenuates the reinstatement of METH-seeking behavior, but these effects may be due to nonspecific suppression of general appetitive behaviors.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalPsychopharmacology
Volume225
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Metabotropic Glutamate 5 Receptor
Methamphetamine
Sucrose
Food
Cues
Pharmaceutical Preparations
Appetitive Behavior
Self Administration
fenobam
Cognitive Therapy
Pharmacology
Recurrence

Keywords

  • Cue
  • Drug prime
  • Food
  • Methamphetamine
  • mGluR5
  • Negative allosteric modulator
  • Reinstatement
  • Sucrose

ASJC Scopus subject areas

  • Pharmacology

Cite this

Attenuation of reinstatement of methamphetamine-, sucrose-, and food-seeking behavior in rats by fenobam, a metabotropic glutamate receptor 5 negative allosteric modulator. / Watterson, Lucas R.; Kufahl, Peter R.; Nemirovsky, Natali E.; Sewalia, Kaveish; Hood, Lauren E.; Olive, Michael.

In: Psychopharmacology, Vol. 225, No. 1, 01.2013, p. 151-159.

Research output: Contribution to journalArticle

Watterson, Lucas R. ; Kufahl, Peter R. ; Nemirovsky, Natali E. ; Sewalia, Kaveish ; Hood, Lauren E. ; Olive, Michael. / Attenuation of reinstatement of methamphetamine-, sucrose-, and food-seeking behavior in rats by fenobam, a metabotropic glutamate receptor 5 negative allosteric modulator. In: Psychopharmacology. 2013 ; Vol. 225, No. 1. pp. 151-159.
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abstract = "Rationale: Methamphetamine (METH) is a highly potent and addictive psychostimulant with severe detrimental effects to the health of users. Currently, METH addiction is treated with a combination of cognitive and behavioral therapies, but these traditional approaches suffer from high relapse rates. Furthermore, there are currently no pharmacological treatment interventions approved by the FDA specifically for the treatment of METH addiction. Objectives: Metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulators (NAMs) have shown promise in significantly attenuating drug self-administration and drug-seeking in reinstatement paradigms. However, studies assessing the potential efficacy of mGluR5 NAMs that have been tested in human subjects are lacking. The current study sought to assess the effect of the mGluR5 NAM fenobam on METH-seeking behavior. Methods: Rats were trained to self-administer METH (0.05 mg/kg i.v.), and following extinction, tested for effects of fenobam (5, 10, or 15 mg/kg intraperitoneal) on cue- and drug-induced reinstatement of METH-seeking. To determine if fenobam also alters reinstatement of seeking of natural reinforcers, separate groups of rats were trained to self-administer sucrose or food pellets and were tested for the effects of fenobam on cue-induced reinstatement of sucrose- and food-seeking. Results: Fenobam attenuated drug- and cue-induced reinstatement of METH-seeking behavior at doses of 10 and 15 mg/kg. Fenobam also attenuated cue-induced reinstatement of sucrose- and food-seeking at all doses tested. Conclusions: The mGluR5 NAM fenobam attenuates the reinstatement of METH-seeking behavior, but these effects may be due to nonspecific suppression of general appetitive behaviors.",
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