Estradiol and striatal dopamine receptor antagonism influence memory system bias in the female rat

•Systemic dopamine D1 and D2 receptor antagonists affect memory system bias in low but not high estrogen rats.•Here we injected D1 and D2 antagonists directly into the dorsal or ventral striatum.•Dorsal, but not ventral, striatal D1 antagonism altered memory system bias.•Systemic D2 antagonism likely affecting memory systems in a different brain area.

Estradiol (E2) has been shown to influence learning and memory systems used by female rats to find a reward. Rats with high levels of E2 tend to use allocentric, or place, memory while rats with low levels of E2 use egocentric, or response, memory. It has been shown that systemic dopamine receptor antagonism interacts with E2 to affect which memory system is used. Here, dopamine antagonists were administered directly into either the dorsal striatum or nucleus accumbens to determine where in the brain this interaction takes place. Seventy-four young adult, female, Sprague-Dawley rats were trained and tested in a modified plus-maze. All rats were ovariectomized, received a subcutaneous low E2 implant, and were implanted with bilateral cannulae into either the dorsal striatum or the nucleus accumbens. Additionally, high E2 rats received daily injections of E2 in a sesame oil solution while low E2 rats received daily injections of vehicle. After reaching criterion levels of performance in a plus-maze task, rats were administered microinjections of either a dopamine D1 receptor (SCH 23390; 0.1 μg/ml and 0.01 μg/ml) or D2 receptor (raclopride; 2 μg/ml and 0.5 μg/ml) antagonist or a vehicle control (saline) in a counterbalanced manner. High E2 rats exhibited a trend towards a place memory bias while low E2 rats showed a response memory bias. Dorsal striatal administration of a D1, but not D2, dopamine receptor antagonist caused a switch in the memory system used by both high and low E rats. There was no significant effect of dopamine receptor antagonism in the nucleus accumbens group. Thus, E2 determined which memory system controlled behavior in a plus-maze task. Moreover, this effect was modulated by dopamine D1R antagonism in the dorsal but not ventral striatum suggesting that memory systems are, in part, mediated by E2 and dopamine in this region.