Memory facilitation produced by dopamine agonists: role of receptor subtype and mnemonic requirements

Abstract

The role of dopamine (DA) receptor subtypes in the acquisition of two memory tasks in the 8-arm radial maze was examined. The receptors were manipulated with posttraining, subcutaneous injections of an indirect DA receptor agonist (D-amphetamine), a selective D2 receptor agonist (LY171555), and a selective D1 receptor agonist (SKF-38393). On a win-stay task (sensitive to caudate nucleus lesions) a light cue signalled the location of food in 4 randomly selected arms on each trial. Rats were given one trial per day and injected after training on day 5. D-Amphetamine (2.0 mg/kg) and LY171555 (2.0 mg/kg) improved performance relative to controls; however SKF-38393 (1-4 mg/kg) had no effect on the acquisition of win-stay behavior. On a win-shift task (sensitive to fornix/hippocampal lesions) a delay of 18 hr was imposed between the first 4 and second 4 choices; drugs were injected after the first 4 choices. D-Amphetamine (1.0 mg/kg) and LY171555 (2.0 mg/kg) significantly improved retention relative to controls. SKF-38393 (1-4 mg/kg) had no effect on win-shift retention. These results suggest that the memory-improving properties of DA agonists on tasks sensitive to both hippocampal and caudate lesions are mediated by the D2 receptor.