A Comparative Study On The Effect Of ABT-418 And Methylphenidate On The Locomotor Activity, Spatal Learning, Anxiety, Non-selective Attention And The Expression Of α₄β₂ Nicotinic Receptor Of SHR: An Animal Model Of ADHD

Objective To investigate the effect of ABT-418 on the locomotor activity, spatial memory, anxiety and non-selective attention on SHR, an animal model of attention-deficit hyperactivity disorder. Method Male SHR were randomly assigned to ABT-418 group(A) , methylphenidate group(B), methylphenidate combined ABT-418 group(C), and control group(D). The rats of group A were injected i.p. ABT-418(0.6mg/kg), group B were injected i.p. with methylphenidate(10mg/kg), group C were injected i.p. with methylphenidate(10mg/kg) combined with ABT-418(0.6mg/kg), group D were injected i.p.with the same volume of saline instead. Open field test, Elevated plus-maze test and Ldt maze test were performed before injection, half an hour and 24 hours later and 7^th and 14^th day. Morris water-maze test were performed at the 14^th day. Results 1. In open field test, group B and group C has significantly reduced rearing times than group D, and has significantly increased stereotyped actions than group A and D 30min after the injection(P<0.05). 24 hours later, group A has marked decrease in grating than group B, C and D. after one week's repeatedly injection, group A, B and C has significantly decrease in grating and rearing times than group D. In stereotyped action, group B and C was significantly higher than group A and group D, and there also a marked difference between group B and groupC. after two weeks' repeatedly injection, group A, B and C has significantly decreased grating than group D, and group A has significantly increase than group B and C. In stereotyped action, group B and group C was significantly higher than groupA and group D, and there also a significant difference between group B and group C. 2. In water maze test, there were no significant difference irj escape latency among A, B, C and D group during the three days of training, but at the test day after training, group A, B and C has significantly increased times of orienting swimming than group D. 3. In elevated plus-maze test, 30mins after the injection, group A has significantly increase in open-arms entries than group B; after two weeks' repeatedly injection, group A has significantly increase in open-arms entries than group B and C. There were no significant difference in open-arms time among group A, B, C and D. 4. In Ldt maze test, group A and C has significant increase in rearing times than group D at 30min after the injection, 7th and 14th day. Group B has significant increase in rearing times than group D at the 7th and 14th day. 5. Factor analysis revealed that there maybe synergistic effect between ABT-418 and methylphenidate on the adjustment of locomotor activity of SHR. Conclusion Injection of ABT-418 in SHR can reduce the grating in open-field test and increase the times of orienting swimming in Morris water maze, also can increase the times of open-arms entries in high plus-maze test and rearing times in Ldt maze. The results suggested that in SHR, administration of ABT-418 can not only reduce its locomotor activity, improve its spatial memory and non-selective attention, but reduces anxiety. Furthermore, there maybe synergistic effect between ABT-418 and methylphenidate on the adjustment of locomotor activity of SHR.