Effects of the Putative Cognitive-Enhancing Ampakine, CX717, on Attention and Object Recognition Memory

Yiwen      Zheng; Sangeeta      Balabhadrapatruni; Chisako      Masumura; Cynthia      L. Darlington; Paul      F. Smith

Abstract

Ampakines are a class of putative nootropic drug designed to positively modulate the AMPA receptor and have been investigated as a potential treatment for cognitive disorders such as Alzheimers Disease. Nonetheless, some ampakines such as CX717 have been incompletely characterized in behavioural pharmacological studies. Therefore, in this study, we attempted to further characterize the effects of the ampakine, CX717 (20 mg/kg s.c), on the performance of rats in a 5 choice serial reaction time (5CSRTT) and object recognition memory task, using rats with cognitive deficits caused by bilateral vestibular deafferentation (BVD) as a model. In the 5CSRTT, when the stimulus duration was varied from 5 to 2 sec, the number of incorrect responses was significantly greater for the BVD group compared to sham controls, but significantly less for the CX717 groups, with no significant interaction. With changes in inter-trial interval (ITI), there was a significant effect of surgery/drug and a significant effect of ITI on premature responses, and the BVD group treated with CX717 showed significantly fewer premature responses than the other groups. In the object recognition memory task, CX717 significantly reduced total exploration time and the exploration towards the novel object in both sham and BVD animals. These results suggest that CX717 can reduce the number of incorrect responses in both sham and BVD rats and enhance inhibitory control specifically in BVD rats, in the 5CSRTT. On the other hand, CX717 produced a detrimental effect in the object recognition memory task.

Keywords: Ampakines, nootropic drugs, cognitive dysfunction, vestibular lesions, rats, vestibulo-spinal reflexes, vestibular dysfunction, BVD surgery