Date Published: April 19, 2019
Publisher: Public Library of Science
Author(s): Hannah Phillips, Arlene McDowell, Birgitte S. Mielby, Ian G. Tucker, Michael Colombo, Giuseppe Biagini.
Understanding the effects of cognitive enhancing drugs is an important area of research. Much of the research, however, has focused on restoring memory following some sort of disruption to the brain, such as damage or injections of scopolamine. Aniracetam is a positive AMPA-receptor modulator that has shown promise for improving memory under conditions when the brain has been damaged, but its effectiveness in improving memory in neurologically healthy subjects is unclear. The aim of the present study was to examine the effects of aniracetam (100mg/kg and 200 mg/kg) on short-term memory in “neurologically healthy” pigeons. Pigeons were administered aniracetam via either intramuscular injection or orally, either 30 or 60 minutes prior to testing on a delayed matching-to-sample task. Aniracetam had no effect on the pigeons’ memory performance, nor did it affect response latency. These findings add to the growing evidence that, while effective at improving memory function in models of impaired memory, aniracetam has no effect in improving memory in healthy organisms.
Cognitive enhancing drugs (nootropics) are drugs that can improve memory and cognition, either by increasing attention or enhancing the mechanism by which memory occurs . Cognitive enhancers are of particular interest as a way to counter disruptions to memory, such as that caused by aging or traumatic brain injury. A less explored avenue of research, however, is the effect of cognitive enhancers on healthy brains. Caffeine is a commonly used cognitive enhancer that improves wakefulness and energy  due to its psychostimulant properties. Other psychostimulants, such as cocaine or methylphenidate (Ritalin), have also demonstrated a facilitative effect on memory-based tasks [3, 4], possibly due to increasing a subject’s ability to focus.
There was no indication that aniracetam improved short-term memory in pigeons, evidenced by a lack of increase in matching accuracy at any of the delays used on the DMS task. Additionally, the absence of any improvement was observed for both the intramuscular and oral delivery routes, and similarly there was no improvement when aniracetam was administered at either 30 or 60 minutes before testing. The lack of improvement was not due to a floor or ceiling performance effect, as the retention functions displayed on the DMS task were ideal for observing any improvement. Finally, the results of the pharmacokinetic study suggest that, at least for the oral administration, we chose the correct testing times in relation to the time-points at which the blood aniracetam and N-anisoyl-GABA concentrations were highest.
Cognitive enhancers are a new and exciting area of research that is rapidly developing. One family of drugs, AMPAkines, show the most potential for cognitive enhancement, via modulation of the AMPA receptor, and with minimal negative side effects. The current study failed to find an improvement in matching accuracy in healthy pigeons after treatment with one such AMPAkine, aniracetam. Matching accuracy did not improve at doses of 100 mg/kg or 200 mg/kg. We tested both oral and intramuscular routes of administration, and tested two different time-points of drug delivery; 30 minutes and 60 minutes prior to testing. We also conducted a pharmacokinetic study to determine the time after oral administration at which blood concentration was highest and found that our chosen testing times were in line with these times. Despite the negative results of the present study, they add to the argument being formed by the current literature that, while effective at restoring memory after experimentally-induced disruption, aniracetam has little effect on memory performance in healthy subjects. What little evidence there is for an improvement in healthy subjects is marginal at best, and is inconsistent in terms of when and how much of the drug should be administered to see an effect.