A Control Study Of The Effect Of α₄β₂ Nicotinic Receptor Competitive Antagonist On Non-selective Attention, Activity, Memory And Expression Of α₄β₂ Receptor Of SHR-an Animal Model Of Attention Deficit Hypera

Part oneThe effect of competitive antagonist of α4β2 nicotinicreceptor on non-selective attention, activity, spatialmemory of SHR- a rat model of attention deficithyperactivity disorderObjective To investigate the non-selective attention, activity, spatial memory effects of dihydro-β-erythroidine ( DHβE ) -a competitive antagonist of α4β2 nicotinic receptor subtype and methylphenidate(MPD) on SHR (spontaneously hypertensive rat, SHR), an animal model of ADHD (attention deficit hyperactivity disorder, ADHD) and to explore the role of nicotinic system in ADHD treatment.Methods Male SHR were randomly assigned to four group, non-selective attention index, activity in open field test, anxiety related behavior, and learning memory skill of rat were tested after 30min, 24h, 7day, 14day of DHpE, MPD, MPD combined DHPE, or saline intraperitoneal (i.p) injected respectively.Results non-selective attention in Ldt-maze test There is no difference of FRE (frequency of rearing episodes, FRE) in Ldt-maze test between each study group and control at 30min, 24h after single dosage and 7^th day ,14^th day after systematic administration (P>0.05). In comparing with the group of MPD+DHβE, the DHβE has lower FRE at 14^th day after the systemic administration (P<0.05). The DRE (duration of rearing episodes, DRE) of DHβE group decreased significantly at 24 hour, 14^th day (P<0.05),meanwhile the DRE increased remarkably at 14th day in group of MPD (PO.05) in compare with the control. Significant difference of DRE were observed between DHpE and MPD at 30min, 24hour, and 7th , 14th day in the executive experimental time(P<0.05).Activity in open field test The horizons movement and rearing episodes was low in group of MPD as well as MPD+DHBE at 30min after the drug administration(P<0.05); In compare with the control, also these two group has higher stereotype movement at each experimental time except 24h after drug administration. There is no difference of activity between DHPE and saline at each time of open field test (P>0.05).Anxiety related behaviors in elevated plus maze test14th day after administration, the group of MPD+DHBE has higher entries and longer duration in open arm than control group and the group of DHPE has less open-arm entries at the same time in contrast with the control group(P<0.05).Spacial memory in Morris water mazeTest performed 10th day after systematic administration in each group, there was no significant statistical difference in the escape latencies between the study group and the control, but remarkably difference was observed in the times of crossing the exact position of the former platform, MPD>MPD+DHBE>saline>DHBE.Conclusion Competitive antagonist of a 4JJ2 nicotinic receptor DHpE may deteriorate the no selective attention dysfunction in SHR but MPD increase the attentive level of SHR. MPD decreased the activity of SHR but increased the stereotype movement meanwhile DHPE did not. MPD showseffective in hyperactivity of SHR, but there is no significante effect on impulsive and anxiety related behavior in SHR; DHBE, when combined with MPD, at lest in partly, deteriorate the anxiety of SHR in the elevated plus-maze. In MWM (Morris water maze, MWM) test, the spacial learning and memory of SHR has improved by MPD but DHpE did not. Part twoThe effect of competitive antagonist of a4p2 nicotinicreceptor on a 4B2 Nicotinic receptor subtype expressionin brain of SHR, an animal model of attention deficithyperactivity disorderObjective To explore the expression level of nicotinic receptor