Changes of protein kinase A expressions in shell of accumbens nucleus during the process of chronic morphine-induced conditioned place aversion in rats

Abstract

Objective To explore neurobiological mechanisms of the withdrawal-induced aversion, the changes of protein kinase A(PKA) were measured in shell of accumbens nucleus (AcbSH) of CPA model rats. Methods 1.All 36 male SD rats were divided into three groups, model group (MN group), and control group (MS group and SN group). MN group was injected with morphine, 6.5 days, 10mg/kg, intraperitoneally (IP), twice per day, naloxone injection, 0.3 mg/kg, ip, along with conditioned place aversion training, to develop the CPA model.The MS group was administrated equivalent volume of morphine and saline.Also the SN group was injected with equivalent volume of saline and naloxone.2.During the development of CPA, the expression of protein kinase A was assayed with immunohistochemistry in the AcbSH. Results Before the development of CPA, PKA expressions were no significant differences among the three groups in the AcbSH (F=2.306, P=0.130). However, after development of CPA , PKA expressions showed significant differences among the three groups(F=36.516, P=0.000). The average gray intensity of MN group (109.50±4.661) was apparently higher than the MS group(126.50±3.697, P<0.01), than the SN group (133.50±6.364, P<0.01). Conclusions 1.Protein kinase A expression, leading to the aversion in the AcbSH probably is a key pathway contributing to the development of CPA.2.The neuroadaptation mediated by PKA may be one of important molecular underpinnings of CPA. Key words: Conditioned place aversion; Protein kinase A; Immunohistochemistry