| BackgroundAttention deficit hyperactivity disorder(ADHD)is one of the most common chronic neurobehavioral disorders in childhood.The increasing number of studies has confirmed that nicotinic acetylcholine receptor(nAChR)has an important role in a number of neuropsychiatric disorders,and the association between smoking and ADHD has been confirmed that nicotine and nicotine subtype-selective agonists have beneficial effects on various aspects of ADHD patients’ cognitive and clinical function.This study explores the impact of nicotinic acetylcholine receptor agonist of ABT-418 and PNU282987 on the behavior and the expression level of α4β2、α7 nicotinic receptor subtype in an animal model of spontaneously hypertensive rat(SHR)in which the hippocamal,prefrontal cortex and corpus striatum were used as the target brain regions.Objectives1.To investigate the effect of nicotinic receptor agonist on the behaviors of SHR,an animal model of attention-deficit hyperactivity disorder.2.To investigate the effect of nicotinic receptor agonist on the expression of α4β2、α7nicotinic receptor in SHR,and to explore the role of nicotinic system in ADHD.Methods1.The grouping of experimental animal.30 SPF male SHR rats were randomly assigned to normal control group,saline,ABT-418,PNU-282987,ABT-418 combined with PNU-282987.The rats in group saline,ABT-418,PNU-282987,ABT-418 combined with PNU-282987 were injected i.p.saline(1ml),i.p.1ml solution of ABT-418(0.6mg/Kg),i.p.1ml solution of PNU-282987(1mg/Kg),i.p.1ml solution of ABT-418(0.6mg/Kg)combinedwith PNU-282987(1mg/Kg),respectively.2.Behavioral assessment.Open field test and Lat maze test were performed before injection and 7d and 14 d after injection,respectively.10 d after injection,the 4-day-Morris-maze test were carried out and the tested was conducted on the last day.3.Experimental.The expression of α4β2 and α7 nicotinic receptor in hippocamal,prefrontal cortex and corpus striatum were detected with immunohistochemistry.The expression level of mRNA in hippocampal,prefrontal and corpus striatum were detected with situ hybridization methods.4.Statistics.The data were analyzed with SPSS20.0 statistical software package.Multiple groups of measurement data were processed in one-way analysis of variance(one-way ANOVA).Once homogeneity of variance was observed,LSD method was applied,or Kruskal-Wallis Test was applied.The difference was considered significant if P<0.05.Results1.Behavioral assessment1.1 In the open field test,there was no significant difference(P>0.05)before the injection among the five groups.The grating times,rearing times and the moving distances in group ABT-418,PNU-282987,ABT-418 combined with PNU-282987 were significantly less than those in control group,saline group after one week repeated injection,but there was no difference in the grooming times.While,the grating times,rearing times,grooming times and the moving distances in group ABT-418,PNU-282987,ABT-418 combined with PNU-282987 were significantly less than those in control group and saline group after two weeks repeated injection.1.2 In Lat maze test,there were no significant differences in the rearing numbers among all groups(P>0.05);the rearing times in group ABT-418,PNU-282987,ABT-418 combined with PNU-282987 were significantly increased than those in control group and saline group at the 7th and 14 th day(P<0.05).1.3 In Morris water maze,there was no significant difference in escape latency among all groups during the four days of training(P>0.05),but at the last test day of training,the times of orienting swimming and the quadrant of the original platform in group ABT-418,PNU-282987,ABT-418 combined with PNU-282987 significantly increased than those in group A and B(P<0.05).2.Compared with control group and saline group,the expression of α4β2 and α7nicotinic receptor protein in hippocampus,prefrontal and corpus callosum of group ABT-418,PNU-282987,ABT-418 combined with PNU-282987 were significant difference(P<0.05),and there was no significant difference among the three groups.3.There were no differences of expression level of α4β2 and α7 nicotinic receptor mRNA in hippocampus,prefrontal and corpus callosum among 5 groups(P>0.05).Conclusions1.The intervention of ABT-418 and PNU-282987 can reduce locomotor activity,and enchance the spatial learning,memory and non-selective attention of SHR.2.The intervention of ABT-418 and PNU-282987 can up-regulate the expression ofα4,β2 and α7 nicotinic receptor protein in hippocampus,prefrontal and corpus callosum,but the differences are not significant at mRNA level.3.ABT-418 and PNU-282987 may exert it effects through α4β2 and α7 nicotinic receptor,and the repeated administration can induce the expression of the nicotinic receptor through post-transcript mechanism. |
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