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

doi:10.1016/j.neuropharm.2012.05.037

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

Psychology

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

Recent findings implicate group II metabotropic glutamate receptors (mGluR_2/3) in the reinforcing effects of psychostimulants and have identified these receptors as potential treatment targets for drug addiction. Here, we investigated the effects of mGluR_2/3 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 mGluR_2/3 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 mGluR_2/3 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 language	English (US)
Pages (from-to)	290-301
Number of pages	12
Journal	Neuropharmacology
Volume	66
DOIs	https://doi.org/10.1016/j.neuropharm.2012.05.037
State	Published - Mar 2013

Keywords

Escalation
Methamphetamine
Reinstatement
mGluR

ASJC Scopus subject areas

Pharmacology
Cellular and Molecular Neuroscience

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10.1016/j.neuropharm.2012.05.037

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@article{80565e153d914a0abc263ffce8aed887,

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

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'.",

keywords = "Escalation, Methamphetamine, Reinstatement, mGluR",

author = "Kufahl, {Peter R.} and Watterson, {Lucas R.} and Nemirovsky, {Natali E.} and Hood, {Lauren E.} and Angel Villa and Casey Halstengard and Nicholas Zautra and Michael Olive",

note = "Funding Information: The authors would like to acknowledge Piroska Barabas, Elisabeth Moore, Corina Lucero, Kaveish Sewalia, Joanne Alonso and Evan Armstrong of Arizona State University for their technical contributions, Dr. R{\'e}mi Martin-Fardon of The Scripps Research Institute for insightful conversations regarding the experimental design, and to Dr. Timothy Cheung and Dr. Federico Sanabria of Arizona State University for helpful comments during the revising of this manuscript. This work was supported by PHS grant DA025606 to MFO. The authors declare that they have no conflict of interest.",

year = "2013",

month = mar,

doi = "10.1016/j.neuropharm.2012.05.037",

language = "English (US)",

volume = "66",

pages = "290--301",

journal = "Neuropharmacology",

issn = "0028-3908",

publisher = "Elsevier Limited",

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T1 - Attenuation of methamphetamine seeking by the mGluR2/3 agonist LY379268 in rats with histories of restricted and escalated self-Administration

AU - Kufahl, Peter R.

AU - Watterson, Lucas R.

AU - Nemirovsky, Natali E.

AU - Hood, Lauren E.

AU - Villa, Angel

AU - Halstengard, Casey

AU - Zautra, Nicholas

AU - Olive, Michael

N1 - Funding Information: The authors would like to acknowledge Piroska Barabas, Elisabeth Moore, Corina Lucero, Kaveish Sewalia, Joanne Alonso and Evan Armstrong of Arizona State University for their technical contributions, Dr. Rémi Martin-Fardon of The Scripps Research Institute for insightful conversations regarding the experimental design, and to Dr. Timothy Cheung and Dr. Federico Sanabria of Arizona State University for helpful comments during the revising of this manuscript. This work was supported by PHS grant DA025606 to MFO. The authors declare that they have no conflict of interest.

PY - 2013/3

Y1 - 2013/3

N2 - 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'.

AB - 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'.

KW - Escalation

KW - Methamphetamine

KW - Reinstatement

KW - mGluR

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JO - Neuropharmacology

JF - Neuropharmacology

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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