COCAINE ENHANCES ST8SIAII MRNA EXPRESSION AND NEURAL CELL ADHESION MOLECULE POLYSIALYLATION IN THE RAT MEDIAL PREFRONTAL CORTEX

摘要

The present study investigated whether cocaine (COC) administration evokes changes in the mRNA and protein levels of neural cell adhesion molecule (NCAM) and poly-sialylated neural cell adhesion molecule (PSA-NCAM) in the medial prefrontal cortex (mPFC) of rats. NCAM/PSA-NCAM is required for neuronal structural plasticity and is constitu-tively expressed in the mPFC. Rats were treated with a single dose of COC (15 mg/kg, i.p.), and mRNA levels of NCAM and the polysialyltransferases ST8Siall and ST8SialV, enzymes involved in polysialylation of NCAM, were measured at 3, 6 and 24 h after COC treatment. At the same time points, the protein levels of NCAM and PSA-NCAM were measured via western blotting. Acute COC injection did not affect mRNA levels of NCAM and ST8SialV, but it increased the mRNA level of ST8Siall 3 h after injection. At the same time point, an increase in PSA-NCAM, but not in NCAM, protein was observed. Morphological studies of PSA-NCAM protein expression patterns (immunocytochemistry/stereology) performed 3 h after COC administration revealed an enhancement of PSA-NCAM immunostaining in perisomatic-like sites and in the length density of PSA-NCAM-positive neuropil. Double immunofluorescence staining showed that PSA-NCAM perisomatic-like sites surround excitatory neurons. We also observed that a single injection of raclopride (0.4 mg/kg) or SCH 23390 (0.5 mg/kg), D2/D3 and D1 dopamine receptors antagonists, respectively, which were ineffective when given alone, abolished the effects of COC administration on mRNA and protein expression. The data in the present study indicate that COC administration may modify constitutive synap-tic plasticity in the mPFC by increasing the NCAM polysialylation in perisomatic innervations of pyramidal neurons via activation of dopamine D1 and D2/D3 receptors.