Memory enhancement by post-training peripheral administration of low doses of dopamine agonists: possible autoreceptor effect.

These experiments examined the effect of post-training injections of low doses of dopamine (DA) agonists on the acquisition of two 8-arm radial maze tasks. On a winstay simultaneous discrimination task, a light cue signaled the location of food in four randomly selected arms on each trial, and animals were required to visit each of the lit arms twice within a trial. Animals received one food trial per day and were injected immediately after training on Day 5. The direct DA receptor agonist, apomorphine (0.05 mg/kg), and the direct D2-DA receptor agonists, LY 177555 (quinpirole: 0.05, 0.1 mg/kg) and B-HT 920 (0.05 mg/kg), all improved acquisition of winstay radial maze behavior relative to saline-injected controls. On a win-shift task, rats were allowed to obtain food from four randomly selected maze arms, followed by a delay period in which they were removed from the maze. Animals were returned to the maze for a retention test in which only those arms that had not been visited prior to the delay contained food. After training on shorter delays, a delay of 18 h was imposed between the first four and second four choices, and DA agonists were injected immediately after the first four choices. Apomorphine, LY 171555, and B-HT 920 (all at 0.05 mg/kg), all improved win-shift retention relative to saline-injected controls. On both tasks, delaying the injections for 2 h post-training eliminated the memory-improving effects of all drugs. The results indicate that post-training administration of DA agonists at doses that may preferentially stimulate autoreceptors improves memory.