It is worth mentioning that cordycepin as an

It is worth mentioning that cordycepin, as an adenosine analogue, is structurally similar to adenosine. A previous study has shown that the anti-apoptotic effects of cordycepin are partially dependent on the activation of A1R [16], and cordycepin increases theta waves power density via nonspecific adenosine tazemetostat australia in rats [17]. These researches indicated that cordycepin may exert potentially biological effects as a nonspecific (or partial) agonist of adenosine receptor. Given that adenosine is mainly through its action on A1R and A2AR to control and integrate cognition functions [7], therefore, we assume that the improvement on learning and memory by cordycepin is likely related to the densities of A1R and A2AR. In order to provide a new window into the pharmacological properties of cordycepin, in the present study, we examined the roles of cordycepin on short-term spatial memory using a spontaneous alternation behavior (SAB) test in Y-maze, and investigated adenosine content and A1R and A2AR densities in hippocampal subregions.
Materials and methods
Results
Discussion The present study found that oral cordycepin treatment improved the percent of relative alternation in the SAB test but did not affect body weight, hippocampus weight and adenosine content in mice. Furthermore, intragastric administration of 10mg/kg cordycepin only decreased the density of A1R in hippocampal DG region, but significantly reduced the density of A2AR in hippocampal DG, CA1 and CA3 areas. SAB always stands for the tendency for rats, mice and other animals to alternate their choices on Y- or T-maze. It has been ascribed to the operation of a variety of mechanism including stimulus satiation, action decrement, curiosity and habituation to novelty and spatial working memory [25]. In recent years, the SAB test has been widely accepted as a quick and relatively simple measure of memory retention because of avoiding the need for extensive training and the use of conventional reinforcers [26]. In the present study, we found that the behavioral activity of mice in the SAB test was closely related to the test time and the sex. With the extension of test time, mice alternation was lowered, as well as an increase in instability. We observed that the percent of relative alternation (short-time memory) and the total number of arm entries (locomotor activity) in mice were well-distributed and stable from 3 to 8min. Our findings were consistent with the literature showing that 5, 8 or 10min in the SAB test were usually set as the test time [21], [22]. Therefore, we recorded the behavioral response from 3 to 8min as the test time in our behavioral experiment. We also found that the female mice showed more exploration (locomotor activity) and curiosity in the novel environment as compared with the male mice, suggesting that estrogen may be helpful for the novel exploration but does not alter the short-term spatial memory. Similarly, the improvement of exploratory behavior in female mice had been observed [27]. Moreover, a previous study has shown that mice, proestrous compared to diestrous wildtype, but not estrogen receptor beta knockout, have better performance in the spontaneous alternation [28]. Although it has been largely proved that estrogen could improve learning and memory [29], [30], the role of estrogen in the modulating the performance on tasks of learning and memory is complex because it exerts enhancing effects on some tasks and impairing effects on others [31]. Hypotheses have been offered to explain these varied results including differentiating the effects of estrogen on cognitive processes required to complete tasks and analyzing the influence of fluctuating levels of estrogen on the strategies selected by animals to solve tasks. Collectively, it is necessary to further measure the level of estrogen in mice to explain the roles of estrogen in the SAB test in future.