Attenuation of methamphetamine seeking by the mGluR2/3 agonist LY379268 in rats with histories of restricted and escalated self-Administration

Peter R. Kufahl, Lucas R. Watterson, Natali E. Nemirovsky, Lauren E. Hood, Angel Villa, Casey Halstengard, Nicholas Zautra, Michael Olive

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Recent findings implicate group II metabotropic glutamate receptors (mGluR2/3) in the reinforcing effects of psychostimulants and have identified these receptors as potential treatment targets for drug addiction. Here, we investigated the effects of mGluR2/3 stimulation on cue- and drug-primed reinstatement in rats with different histories of methamphetamine (METH) self-Administration training, under two conditions: 16 daily sessions of short access (90 min/day, ShA), or 8 daily sessions of short access followed by 8 sessions of long access (6 h/day, LgA). Following self-Administration and subsequent extinction training, rats were pretreated with the selective mGluR2/3 agonist LY379268 (variable dose, 0-3 mg/kg), exposed to METH-paired cues or a priming injection of METH (1 mg/kg), and tested for reinstatement of METH-seeking behavior. LgA rats self-Administered greater amounts of METH during the second half of training, but when pretreated with vehicle, ShA and LgA rats showed cue- and drug-primed reinstatement at equivalent response rates. However, LgA rats demonstrated greater sensitivity to mGluR2/3 stimulation with attenuated responding during cue-induced reinstatement after 0.3 mg/kg and higher doses of LY379268, whereas ShA rats decreased cue-induced reinstatement behavior following 1.0 mg/kg and 3.0 mg/kg LY379268. Additionally, both LgA and ShA rats exhibited decreased METH-primed reinstatement behavior following 0.3 mg/kg and higher doses of LY379268. A separate group of control rats was trained to self-Administer sucrose pellets, and demonstrated attenuated cue-induced sucrose-seeking behavior following 1.0 and 3.0 mg/kg LY379268. Together, the results indicate that LY379268 has differential attenuating effects on cue-induced reinstatement behavior in rats with different histories of METH intake. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.

Original languageEnglish (US)
Pages (from-to)290-301
Number of pages12
JournalNeuropharmacology
Volume66
DOIs
StatePublished - Mar 2013

Keywords

  • Escalation
  • Methamphetamine
  • Reinstatement
  • mGluR

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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