The Therapeutic Effects Of H1 Mediated IL2 Nanoparticles (H1/pIL2) On The Methamphetamine-induced Drug Addiction In Rat Model

Objective:To establish MA dependent rat model, then injected H1 mediated IL2 nanoparticles (H1/PIL2) into the lateral cerebral ventricle of MA dependent rats. Through the behavior change of rats, the expression of interleukin-2 in the rat brain and the change of nucleus accumbens dopamine content to explore the effect of H1 mediated IL2 nanoparticles on the MA dependent rats. Methods:Though plasmid amplification method to get a large amount of IL2 plasmid and GFP plasmid. Then the vector H1 respectively combined with IL2 plasmid and GFP plasmid, synthesis H1 mediated interleukin-2 nanoparticles (H1/PIL2) and H1 mediated green fluorescent protein nanoparticles (H1/EGFP).95 SD rats were divided into control groups(N=20), and establish different rat model of different dependent time courses which were one-week(N=25), four weeks(N-25) and eight-weeks(N=25). Three dependent groups were divided into four subgroups, respectively, MA dependent group(N=21), MA dependent+ sham-operated group(N=18), MA dependent+H1/EGFP group(N=18), MA dependent+Hl/PIL2 group(N=18). Use the stereotaxic instrument to locate the lateral ventricle accurately. Used dental drill to craniotomy and drilling, injected H1-mediated interleukin-2 nanoparticles in rats ventricle of MA dependent+Hl/PIL2 group (100ul,2 times/week). MA dependent+H1/EGFP group injected H1 mediated green fluorescent protein nanoparticles(100ul,2 times/week). The conditioned place preference(CPP) test and stereotyped behavior scores were performed to measure the rats withdrawal syndromes. The ELISA methods were used to detect the human interleukin-2 content in six brain regions of rats and nucleus accumbens dopamine content changes.Results:1. after were injecting with MA, the time that the rat stayed at the side of the non-preference was extended, and stereotyped behavior was significantly performed.2. MA dependent+Hl/PIL2 group, one week group and four weeks group, the time that the rat stayed at the side of the non-preference was significantly shorter; But the time did not change significantly for eight weeks group.3. Compared with the dependent group, after H1/PIL2 intervention, there were significant differences in the stereotyped behaviors scores for one-week, four-week groups and eight-week groups, respectively(P<0.05).4. MA dependence+H1/PIL2 group, human interleukin-2 contents of substantia nigra, striatum, nucleus accumbens, compared with MA dependent group were significantly higher(P<0.05); the human interleukin-2 contents of prefrontal cortex and ventral midbrain, compared with MA dependent group did not change significantly (P> 0.05).5 As for MA dependent+H1/PIL2 group, the dopamine contents changed significantly compared with MA dependent group and MA dependent+Hl/EGFP group. Conclusion:1. the model of MA dependence rat is established by intraperitoneal injection of several times and conditioned placed reference.2. MA dependent+H1/PIL2group, the psychological dependence symptoms of MA depend rats alleviated, and stereotyped dependent behavior improved.3. Intraventricular injection of H1/PIL2 one week group, the expression of IL2 contents in substantia nigra, striatum, nucleus accumbenswere significantly higher. In prefrontal cortex and ventral midbrain, which did not significantly change. It was significant reduction in the hippocampus as well.4. After intracerebroventricular injection, the dopamine contents of one week group and four week group had significant increase in the nucleus accumbens. The data indicated that interleukin-2 might not be activated by methamphetamine nucleus accumbens septi dopaminergic pathway, but played a role though acting the function of other neurotransmitters in the nucleus accumbens septi.