Extinction of a cocaine-taking context that protects against drug-primed reinstatement is dependent on the metabotropic glutamate 5 receptor.
We investigated the effects of extinguishing action-reward versus context-reward associations on drug-primed reinstatement, and the potential role of the metabotropic glutamate 5 receptor (mGlu5) in these different types of extinction in rats that self-administer cocaine. We observed that daily context extinction (non-reinforced exposures to the cocaine-taking context with retracted levers) was just as effective as daily lever extinction in reducing cocaine-primed reinstatement compared with passive abstinence. Additionally, systemic injections of the mGlu5 negative allosteric modulator MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine) following each extinction session significantly impaired the ability of context extinction to reduce cocaine-primed reinstatement, without affecting reinstatement after lever extinction or passive abstinence.
Behavioural Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Australia; Florey Department of Neuroscience and Mental Health, University of Melbourne, Australia.
Jee Hyun
JH
Kim
Christina
C
Perry
Sophia
S
Luikinga
Isabel
I
Zbukvic
Robyn M
RM
Brown
Andrew J
AJ
Lawrence
D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D058999:Drug-Seeking Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors / Q000502:physiology*; D012008:Recurrence; D012201:Reward; D012646:Self Administration; D013844:Thiazoles / Q000494:pharmacology
C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D018765:Dopamine Uptake Inhibitors; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D013844:Thiazoles; D003042:Cocaine
Abstinence; MTEP; addiction; context; extinction; mGlu5