Role Of Dopamine D1 Receptors In The Hippocampal Dentate Gyrus On Active Avoidance Learning In Rats

The hippocampus participates the regulation of several higher order brain functions,including learning and memory.Hippocampus is mainly divided into the CA1,CA2,CA3,and dentate gyrus(DG),and as the entry point of information into the hippocampus,the hippocampal DG encodes and processes new information and plays an essential role in learning and memory.Long-term potentiation(LTP)is believed to underlie hippocampus-dependent learning and memory,and the induction and maintenance of LTP is typically dependent on the glutamatergic system.Dopamine(DA)is an important neurotransmitter in the brain,and the hippocampus receives dopaminergic projections mainly from the midbrain,including the retrorubral area,the substantia nigra,and the ventral tegmental area.There are many lines of evidence showing that DA and D1 receptor in the hippocampal CA1 play an important modulatory role in LTP formation and maintenance as well as several learning and memory processes.It has been reported that dopaminergic projections and D1 receptors are found in DG but the effects of DA and D1 receptors in DG on active avoidance learning in rats are unclear.Therefore,in this study,we used an in vivo brain microdialysis and HPLC technique to determine DA release in the DG region during active avoidance conditioned reflex.Then,the antagonist of D1 receptors(SCH-23390)was microinjected into the DG region,and its effects on Glu concentration and synaptic efficiency in the DG during active avoidance learning were investigated.The experimental results are as follows:1.During active avoidance learning,the rate of active avoidance was gradually increased and rats reached the acquisition criterion on the 5th day,after which the extinction procedure was carried out immediately and rats reached the criterion of extinction on the 7th day.Moreover,extracellular levels of DA in the DG region were significantly increased during the acquisition of the active avoidance behavior,which reached to 547,58±60.88%of before starting on the 5th day(P<0.05 vs first day),and it gradually returned following extinction training.In contrast,extracellular levels of DA in the DG region were not significantly changed in non-behavioral test group.2.In the control group,extracellular levels of Glu and fEPSP amplitudes in the DG region were significantly increased during the acquisition of the active avoidance behavior,which reached to 217.00±30.93%and 157.31±21.14%of first day levels on 5th day(P<0.05,respectively),and gradually returned following extinction training.3.In SCH-23390 group,rats did not acquire the conditioned reflex,and Glu levels and fEPSP amplitude in the DG were not significantly changed during behavioral training.Conclusions:DA in the hippocampal DG facilitates active avoidance learning via activation of D1 receptors,and which is associated with the enhancements of glutamate level and synaptic efficiency in rats.