Expression of protein kinase A and the kappa opioid receptor in selected brain regions and conditioned place aversion in morphine-dependent rats

This study examined adaptive changes in protein kinase A (PKA) and kappa opioid receptor (KOR) in selected addiction-related brain regions before and after conditioned place aversion (CPA). Seventy-two male SD rats were randomly assigned to an experimental group (morphine + naloxone, “MN”) and 2 control groups: MS (morphine + saline) and SN (saline + naloxone). MN rats were intraperitoneally injected with morphine twice per day for 6.5 days and naloxone once and trained to establish CPA model. MS and SN rats were injected with equivalent volumes of morphine plus saline and saline plus naloxone, respectively. PKA and KOR in AcbSH, CeA and VTA were measured by immunohistochemistry. Before CPA, there were no significant differences in PKA and KOR expression levels in the AcbSH, CeA and VTA between MN and 2 control groups. After CPA, significant differences in PKA expression were detected in the AcbSH (P<0.001) and VTA (P=0.018) between MN and 2 control groups. The average gray intensity of MN group (109.50±4.66) in AcbSH was significantly higher than that of MS (126.50±3.70, P<0.001) and MN (133.50±6.364, P<0.001) groups. Significant differences in KOR expression were also detected between MN and 2 control groups in CeA (P<0.001). In MN group, PKA and KOR expression levels showed adaptive changes at different points of CPA. These findings demonstrated that neuroadaptation mediated by PKA and KOR may be an important molecular neurobiology basis for CPA. The upregulation of AC-cAMP-PKA-CREB signaling pathway in AcbSH and VTA has some role in the neurobiological mechanism of CPA.