Memory enhancement in mice: role of drug dose and training-testing interval

Pharmacologic probes are useful for studying memory mechanisms. For eight drug treatments affecting a variety of transmitter systems [arecoline, piribedil, clonidine, fluoxetine, naloxone, ACTH (4-10)], we determined how long memory retention would remain improved with a dose sufficient to improve 3-hour retention. While all 6 treatments enhanced 3-hour retention test performance at p less than 0.05, only 5 treatments significantly enhanced retention 24 hour after training and none of the treatments significantly affected retention at 168 hours. A detailed analysis of the dose and retention interval interaction for arecoline indicated that at low doses retention decreased as the retention interval increased while higher doses improved retention up to 3 hours and only the highest dose tested enhanced retention at 3 and 24 hours. Drug doses that enhance short-term retention (3 hours) were not adequate to enhance long term retention (168 hours). The 6 drug treatments had no significant or systematic effect on activity or on acquisition. We conclude that short-term retention performance was better because of enhanced memory processing or recall and not because of performance effects per se.