Attenuation of methamphetamine seeking by the mGluR2/3 agonist LY379268 in rats with histories of restricted and escalated self-administration.
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'.
Department of Psychology, Arizona State University, PO Box 871104, Tempe, AZ 85287-1104, USA. peter.kufahl@asu.edu
Peter R
PR
Kufahl
Lucas R
LR
Watterson
Natali E
NE
Nemirovsky
Lauren E
LE
Hood
Angel
A
Villa
Casey
C
Halstengard
Nicholas
N
Zautra
M Foster
MF
Olive
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000502:physiology; D012055:Reinforcement Schedule; D012646:Self Administration / Q000523:psychology; D013395:Sucrose / Q000494:pharmacology
D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D000697:Central Nervous System Stimulants; D018690:Excitatory Amino Acid Agonists; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D008694:Methamphetamine; D013395:Sucrose