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mGluR2/3 mediates short‐term control of nicotine‐seeking by acute systemic N‐acetylcysteine
Author(s) -
Moro Federico,
Orrù Alessandro,
Marzo Claudio Marcello,
Di Clemente Angelo,
Cervo Luigi
Publication year - 2018
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12443
Subject(s) - nicotine , pharmacology , metabotropic glutamate receptor 2 , glutamate receptor , metabotropic glutamate receptor , nucleus accumbens , psychology , self administration , saccharin , metabotropic receptor , antagonist , chemistry , anesthesia , medicine , neuroscience , receptor , central nervous system
Chronic self‐administration of nicotine induces maladaptive changes in the cortico‐accumbal glutamate (Glu) network. Consequently, re‐exposure to nicotine‐associated cues raises extracellular Glu in the nucleus accumbens reinstating drug‐seeking. Restoring basal concentrations of extracellular Glu, thereby increasing tonic activation of the presynaptic group II metabotropic Glu receptors (mGluR2/3) with N‐acetylcysteine (N‐AC), might offer a valid therapeutic approach for maintaining smoking abstinence. Although N‐AC modulates nicotine‐seeking behavior by drug‐associated stimuli in abstinent rats, it is still unclear whether it occurs through activation of mGluR2/3. Male Wistar rats were trained to associate discriminative stimuli (S D s) with the availability of intravenous nicotine (0.03 mg/kg/65 µl/2‐second/infusion) or oral saccharin (100 µl of 50 mg/l) self‐administration versus non‐reward. Reinforced response was followed by a cue signaling 20‐second time‐out (CSs). Once the training criterion was met, rats underwent lever press extinction, without reinforcers, S D s and CSs. Re‐exposure to nicotine or saccharin S D+ /CS + , but not non‐reward S D− /CS − , revived responding on the previously reinforced lever. Acute N‐AC, 100 but not 60 or 30 mg/kg i.p., reduced cue‐induced nicotine‐seeking. N‐AC 100 mg/kg did not modify cue‐induced saccharin‐seeking behavior or influenced locomotor activity. Blocking mGluR2/3 with the selective antagonist LY341495, 1 mg/kg i.p., completely prevented the antirelapse activity of N‐AC. The finding that N‐AC prevents cue‐induced nicotine‐seeking by stimulating mGluR2/3 might indicate a therapeutic opportunity for acute cue‐controlled nicotine‐seeking. Future studies could evaluate the persistent effects of chronic N‐AC in promoting enduring suppression of nicotine‐cue conditioned responding.