Gene Expression Profile of Calcium/Calmodulin-Dependent Protein Kinase IIα in Rat Spinal Cord and Midbrain During Induction of Morphine Analgesic Tolerance

Calcium/calmodulin-dependent protein kinase IIα (CamKIIα) may modulate the function of mu-opioid receptors by phosphorylation and therefore, be involved in development of morphine-induced analgesic tolerance. The current study aimed to examine changes in gene expression of CamKIIα in the lumbosacral cord and midbrain during induction of morphine analgesic tolerance. Male Wistar rats weighing 250 - 300 g were used. Two groups of rats (n = 6 per group) received saline (1 mL/kg) or morphine (10 mg/mL/kg) twice-daily for eight days, and induction of morphine analgesic tolerance was assessed using a hotplate test on days one, four and eight of the injections. The lumbosacral spinal cord and midbrain were also dissected in six independent groups (n = 4 per group) on days one, four and eight of saline or morphine injections to examine changes in gene expression of CamKIIα with a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) method. The result of the hotplate test showed that the rats receiving repeated injections of morphine developed tolerance and exhibited significant decrease in antinociception on days four and eight of the injections compared to that of day one (P < 0.001). The result of gene expression in the lumbosacral cord showed no significant changes in the CamKIIα gene expression on days one and eight but its expression significantly increased by 102 % on day four of the injections (P < 0.01). In addition, the CamKIIα gene expression in the midbrain showed no significant changes on days one and four, but it significantly decreased by 67 % on day eight of morphine injection (P < 0.01). It can be concluded that changes in the CamKIIα gene expression in the lumbosacral cord and midbrain during repeated injections of morphine may be differently associated with induction of morphine tolerance.