DOPAMINE D2/D3 RECEPTOR ACTIVATION PROMOTES HIPPOCAMPAL LTD, AND SUPPRESSES LTP IN FREELY BEHAVING RATS

Dopamine D2/D3 receptors (D2/D3R are negatively coupled to adenylyl cyclase and when activated intracerebrally, reduce basal synaptic transmission, in a dose-dependent manner, in the hippocampus of freely behaving rats (doi:10.1093/cercor/13.2.123). Pharmacological antagonism of D2R, in a dose that does not affect basal synaptic transmission, impairs long-term potentiation (LTP) and short-term depression (STD) at Schaffer collateral (SC)-CA1 synapses of the dorsal hippocampus of freely behaving rats, as well as impairs cumulative spatial memory (doi:10.3389/fnbeh.2021.803574). The extent to which dopamine D3R contribute to these processes is unclear.
Here, we treated adult male rats, intracerebrally, with an agonist of D2/D3R (noraporphine) whilst recording from SC-CA1 synapses during free behavior. Both short-term potentiation (STP) and LTP were impaired compared to vehicle-treated controls. STD was prolonged into LTD by the presence of the agonist. Intracerebral treatment with the selective D2R antagonist, remoxipride, prior to noraporphine application, resulted in LTP that did not differ from controls. The facilitation of STD into LTD by noraporphine was unaffected by remoxipride. These data reveal a functional differentiation of the roles of D2/D3R in hippocampal synaptic plasticity: whereas activation of D2R impairs LTP, activation of D3R promotes the expression of LTD.
Acknowledgement: This study was funded by a research grant from the Deutsche Forschungsgemeinschaft to DMV (SFB1280/A04, project no.: 316803389).