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A single high dose of cocaine induces behavioural sensitization and modifies mRNA encoding GluR1 and GAP‐43 in rats
Author(s) -
Grignaschi Giuliano,
Burbassi Silvia,
Zennaro Eleonora,
Bendotti Caterina,
Cervo Luigi
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2004.03712.x
Subject(s) - nucleus accumbens , ventral tegmental area , sensitization , ampa receptor , neuroscience , glutamate receptor , basolateral amygdala , synaptic plasticity , hippocampus , pharmacology , amygdala , chemistry , medicine , psychology , receptor , dopamine , dopaminergic
Neuroadaptive changes underlying repeated exposure to cocaine‐induced behavioural sensitization have been related to modification in the pattern of synaptic connectivity and excitatory transmission. Remarkably, even a single exposure to abused drugs is sufficient to elicit lasting behavioural sensitization. The present study investigated whether in Sprague–Dawley rats a single, behavioural sensitizing dose of cocaine is sufficient to induce changes in the mRNA levels of growth‐associated protein 43 (GAP‐43), an important protein in mediating experience‐dependent plasticity and synaptic reorganization, and of glutamate receptor 1 (GluR1), a subunit of AMPA glutamate receptors, a protein that is up‐regulated with repeated cocaine. Single exposure to 20, but not 10 mg/kg cocaine induced locomotor sensitization to a second injection of 10 mg/kg cocaine, observed at 24 h, 48 h and 7 days. Single dose of 20 but not 10 mg/kg cocaine 48 h before scheduled death significantly enhanced GluR1 and GAP‐43 mRNA expression in the nucleus accumbens (NAc), both shell and core subregions, and ventral tegmental area (VTA). No changes were found in the levels of mRNA for GluR1 and GAP‐43 in the frontal cortex, caudate putamen, dentate gyrus of hippocampus and basolateral nucleus of the amygdala after the single dose of 20 mg/kg cocaine. These results further strengthen the involvement of NAc and VTA in the behavioural sensitization and suggest a role of GAP‐43 in the synaptic reorganization associated to drug abuse.