Lasting reduction of nicotine-seeking behavior by chronic N-acetylcysteine during experimental cue-exposure therapy.
Acetylcysteine
/ pharmacology
Animals
Behavior, Animal
Cues
Drug-Seeking Behavior
/ drug effects
Extinction, Psychological
Free Radical Scavengers
/ pharmacology
Glutamic Acid
/ metabolism
Implosive Therapy
Male
Nicotine
/ administration & dosage
Nicotinic Agonists
/ administration & dosage
Nucleus Accumbens
/ drug effects
Rats
Receptors, AMPA
/ drug effects
Recurrence
Tobacco Use Disorder
N-acetylcysteine
drug-associated cues
nicotine-seeking behavior
Journal
Addiction biology
ISSN: 1369-1600
Titre abrégé: Addict Biol
Pays: United States
ID NLM: 9604935
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
01
08
2018
revised:
10
02
2019
accepted:
09
04
2019
pubmed:
28
5
2019
medline:
29
6
2021
entrez:
28
5
2019
Statut:
ppublish
Résumé
Nicotine-associated cues can trigger reinstatement in humans as well as in animal models of drug addiction. To date, no behavioral intervention or pharmacological treatment has been effective in preventing relapse in the long term. A large body of evidence indicates that N-acetylcysteine (N-AC) blunts the activation of glutamatergic (GLUergic) neurons in the nucleus accumbens (Nacc) associated with reinstatement. We evaluated the effect of an experimental cue exposure therapy (eCET) alone or in combination with N-AC to verify whether restoring GLU homeostasis enhances extinction of nicotine-associated cues. Rats were trained to associate discriminative stimuli with intravenous nicotine or saline self-administration. Reinforced response was followed by cue signals. After rats met the self-administration criteria, the lasting anti-relapse activity of i.p. N-AC or vehicle was assessed in three different experimental conditions after 14 days of treatment: treatment + eCET; treatment + lever-presses extinction (LP-EXT); and treatment + abstinence. N-AC 100 mg/kg, but not 60 mg/kg, induced anti-relapse activity that persisted 50 days after treatment only when paired with either LP-EXT or eCET with the greater activity found in the latter condition. To identify potential mechanisms for behavioral results, separate groups of rats that received either N-AC or vehicle + eCET were killed at different time points for Nacc Western-blot analysis. Seven days after treatment, chronic N-AC restored the expression of proteins crucial for GLU homeostasis, while at 50 days, it increased the expression of type II metabotropic GLU receptors. These results suggest that N-AC treatment in combination with eCET may offer a novel strategy to prevent relapse in nicotine addiction.
Substances chimiques
Free Radical Scavengers
0
Nicotinic Agonists
0
Receptors, AMPA
0
Glutamic Acid
3KX376GY7L
Nicotine
6M3C89ZY6R
glutamate receptor ionotropic, AMPA 2
P6W5IXV8V9
Acetylcysteine
WYQ7N0BPYC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12771Informations de copyright
© 2019 Society for the Study of Addiction.
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