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 (IP3 ), 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 IP3 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.
Keywords: glutamate; locomotor activity; nicotine; protein kinase; ventral striatum.
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