Repeated cocaine administration increases B-cell leukemia/lymphoma 2 phosphorylation in the rat dorsal striatum

Protein phosphorylation caused by drug administration is a critical step in the regulation of behavioral alterations. This study was conducted to determine how repeated exposure to cocaine phosphorylates B-cell leukemia/lymphoma 2 (Bcl2), which may be responsible for the regulation of behavioral alterations in the rat dorsal striatum. The results revealed that repeated systemic injections of cocaine (20 mg/kg) once a day for 7 consecutive days increased the phosphorylation of Bcl2 at serine 70 (Bcl2-S70). However, this increase was reduced by the blockade of dopamine D1 receptors, group I metabotropic glutamate receptors (mGluRs), and N-methyl-d-aspartate (NMDA) receptors. In addition, elevation of behavioral locomotor activity after repeated exposure to cocaine was partially reduced by the inhibition of Bcl2. These data suggest that stimulation of dopamine D1 receptors, group I mGluRs, and NMDA receptors following repeated cocaine administration is necessary for the induction of Bcl2-S70 phosphorylation, which contributes to the expression of behavioral sensitization.