A single high dose of cocaine induces behavioural sensitization and modifies mRNA encoding GluR1 and GAP-43 in rats.
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.
Grignaschi
Giuliano
G
Istituto di Ricerche Farmacologiche 'Mario Negri' Via Eritrea 62, 20157 Milan, Italy.
Burbassi
Silvia
S
Zennaro
Eleonora
E
Bendotti
Caterina
C
Cervo
Luigi
L
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D019922:GAP-43 Protein; D012333:RNA, Messenger; D018091:Receptors, AMPA