The Effects Of Immune Challenge Induced By Poly I:C On Morphine-induced CPP In Rats

Drug abuse is a chronic and highly relapsing complicated brain diease. high percent of drug users carry at least one of infections; most of trouble is that caused by RNA viruses, including human immunodeficiency virus (HIV) and hepatitis C virus (HCV). We deem that immune stress activated by HIV and HCV can increase the susceptibility of opiate drug addiction and the difficulty of abstinence. DSRNA polyinosinic-polycytidylic acid (Poly I:C) would be used to mimic the immune challenge induced by HIV/HCV, while the model that Morphine-induced CPP in Rats of rat should also be utilize to investigate the effects of the immune challenge on susceptibility of addiction and relapse.Results: (1) Compared with other groups, injection of Poly I:C in the extinction can slow down the extinction of CPP(D20,P < 0.05); (2) Three hours after intraperitoneal injection of polyinosinic- polycytidylic acid (Poly I:C, 1 mg/kg), the body temperature of animal was significantly influenced[ F(1,18) = 4.912, P = 0.040]; (3) 8-day intraperitoneal injection of polyinosinic-polycytidylic acid (Poly I:C, 1 mg/kg) in a row, the body temperature of animal was not significantly influenced[ F(1,22) = 2.480, P = 0.130]; (4) Injection of Poly I:C before training had no evident effects on the acquisition of rat's morphine CPP[F(1,22) = 0.028,P = 0.868 ]; (5) The injection of PloyI:C in the training of rat's morphine can enhance expression of CPP[ F(1,18) = 4.622, P = 0.045], and speed up the progress of extinction of CPP, but has no significant effets on the reinstatement of CPP when they were gave a single injection with Poly I:C after extinction[ F(1,18) = 0.022, P = 0.884]; (6) Repeatedly injection of Poly I:C in the extinction can slow down the extinction of CPP[F(1,14) = 4.607, P= 0.049]; but have no significant effects on reinstatement of CPP after morphine priming (P = 0.979); (7) Injection of Poly I:C after extinction, have no significant effects on reinstatement of CPP after morphine priming (P = 0.496) ; (8) Repeatedly injection of Poly I:C after extinction can not reinstate of CPP[ F(1,30) = 0.068, P = 0.797].The results show that:(1) It's feasible to choose Poly I:C as immunomodulator for the experiment; (2) About three hours after intraperitoneal injection of Poly I:C (1 mg/kg), the immune challenge has been induced, and after many times injection of the drug, the other functions of rats have not been significantly influenced; (3) Injection of Poly I:C before training had no evident effects on the acquisition of rat's morphine CPP; (4) The injection of PloyI:C in the training of rat's morphine can enhance expression of CPP, and speed up the progress of extinction of CPP;(5) Repeatedly injection of Poly I:C in the extinction can slow down the extinction of CPP , but have no significant effects on reinstatement of CPP after morphine priming; (6) Injection of Poly I:C after extinction can not reinstate of CPP, and has no significant effects on reinstatement of CPP after morphine priming.Because Poly I:C just mimics the general pathogenic patterns of RNA viruses to stimulate the immune system, our present study gives the implication that immune challenge induced by viruses can increase the susceptibility of opiate drug addiction and the difficulty of abstinence, but we have not find the effects on the relapse after withdrawal. Our finding shows that the combination of Poly I:C and opiates is a"selected"model to clarify the profile of immune challenge by virus on opiate addiction, revealed another side of bi-directional causality in the comorbidity of opiate addiction and HIV or HCV infection, and it's of great significance for understand the effects of immune system on drug addiction.