Dopamine D2 receptor and transptor mechanism in the prefrontal cortex of the susceptibility to heroin addiction

Abstract

Objective To establish the rats model of different susceptibility of heroin addiction,and to explore the possible dopamine D2 receptor (D2R) and dopamine transptor (DAT) mechanism leading to the different susceptibility. Methods 130 male SD rats were carried out CPP training,and the rats were randomly assigned into heroin exposure group (n = 100) and saline control group (SC, n = 30). Heroin exposure group were re-classified into two groups according to the numerical value of the CPP-Pre (the testing score minus that of the pretest):high preference group(HP group) and low preference group(LP group) ,each accounting for 30% of the total rats.The D2R and DAT protein expression of high and low preference group and saline control group rats were detectedwith immunohistochemical method in PFC at 30 minutes and on the 1st,3rd,7th, 14th days after the last injection(149.33 ±2.51 vs 135.83 ±1.78 vs99.33 ±2.84,141.83 ±2.50 vs 131.67 ± 1.87 vs99.17 ±3.61,132.83 ±2.40 vs 122.00 ±2.67 vs 100.33 ±4.26,125.67 ±2.22 vs 113.17 ±2.81 vs 98.33 ±3.25,116.86 ± 1.94 vs 108.63 ± 2.31 vs 98.17 ± 3.82 , respectively, P＜0.05). The D2R protein expressions of HP rats were significantly lower than those of the LP and control group rats (P ＜ 0. 05), and those of LP rat were than lower than those ferent among three groups on addiction phase and 1st,3rd days after the last injection of heroin respectively, respectively (P ＜ 0. 05). The DAT protein expressions of HP and LP rats were significantly lower than those of controlgroup rats (P＜ 0. 05). At all testing time-points, the DAT protein expressions had no significant difference betweenHP and LP group(P＞0. 05). Conclusion D2R and DAT of the rats show appears down-regulation in the PFC after chronic heroin exposure. Different individuals have different D2R sensitivity or receptor levels ,and lower D2R related to the high susceptibility to heroin. Susceptibility to heroin addiction may not be directly related to the expression of DAT. Key words: Heroin; Dopamine D2 receptor; Dopamine transport; Prefrontal cortex