Post-adrenalectomy changes in the gene expression of specific G-protein subunits involved in morphine sensitization

Abstract

There are some reports indicating that adrenalectomy significantly potentiates morphine-induced analgesia. Since G-protein subunits have an important role in morphine effects at the cellular level and the exact mechanism(s) of adrenalectomy-induced morphine sensitization has not yet been clarified, the present study was designed to determine the changes in the levels of Galphai/o, Galphas, Gbeta mRNA involved in this phenomenon. All experiments were carried out on male Wistar rats. The tail-flick test was used to assess the nociceptive threshold and corticosterone levels were measured by radioimmunoassay as a marker of HPA function. The dorsal half of the lumbar spinal cord was assayed for the expression of G-protein subunits using semiquantitative PCR normalized to beta-actin gene expression. Results showed that morphine not only in 3 mg/kg, but also in a sub-effective dose (2 mg/kg) could affect the nociceptive threshold and induce an analgesic response in adrenalectomized (ADX) rats while 2 mg/kg morphine did not demonstrate analgesic properties in sham-operated animals. These effects were reversed with corticosterone replacement. Morphine increased plasma corticosterone concentration in a dose-dependent manner in sham-operated rats. Following adrenalectomy a significant increase in the mRNA levels of Galphai/o (79%) and Gbeta (96%) was observed in the dorsal portion of the lumbar spinal cord. In contrast, no significant changes were observed in the mRNA level of Galphas. In conclusion, our results demonstrate that the levels of the cellular components involved in morphine analgesia significantly increase in ADX animals. This may be at least partly responsible for adrenalectomy-induced morphine sensitization.