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Repeated nicotine exposure increases the intracellular interaction between ERK‐mGluR5 in the nucleus accumbens more in adult than adolescent rats
Author(s) -
Yang Ju Hwan,
Sohn Sumin,
Kim Sunghyun,
Kim Jieun,
Oh Jeong Hwan,
Ryu In Soo,
Go Bok Soon,
Choe Eun Sang
Publication year - 2021
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.12913
Subject(s) - metabotropic glutamate receptor 5 , nucleus accumbens , nicotine , metabotropic glutamate receptor , mapk/erk pathway , pharmacology , chemistry , metabotropic glutamate receptor 1 , metabotropic receptor , endocrinology , medicine , striatum , glutamate receptor , receptor , kinase , biochemistry , dopamine
Intracellular interactions between protein kinases and metabotropic receptors in the striatum regulate behavioral changes in response to drug exposure. We investigated the difference in the degree of interaction between extracellular signal‐regulated kinase (ERK) and metabotropic glutamate receptor subtype 5 (mGluR5) in the nucleus accumbens (NAc) after repeated exposure to nicotine in adult and adolescent rats. The results showed that repeated exposure to nicotine (0.5 mg/kg/day, s.c.) for seven consecutive days increased ERK phosphorylation more in adults than in adolescents. Furthermore, membrane expression of mGluR5 in gamma‐aminobutyric acid (GABA) medium spiny neurons was higher in adults than adolescents as a result of repeated exposure to nicotine. Blockade of mGluR5 with MPEP (0.5 nmol/side) decreased the repeated nicotine‐induced increase in ERK phosphorylation. Either blockade of mGluR5 or inhibition of ERK with SL327 (150 nmol/side) decreased the repeated nicotine‐induced increase in the level of inositol‐1,4,5‐triphosphate (IP 3 ), a key transducer associated with mGluR5‐coupled signaling cascades. Similarly, interference of binding between activated ERK and mGluR5 by the blocking peptide, Tat‐mGluR5‐i (2 nmol/side), decreased the repeated nicotine‐induced increases in IP 3 and locomotor activity in adults. These findings suggest that the intracellular interaction between ERK and mGluR5 in the NAc is stronger in adult than in adolescent rats, which enhances the understanding of age‐associated behavioral changes that occur after repeated exposure to nicotine.