Regulation of depotentiation and long-term potentiation in the dentate gyrus of freely moving rats by dopamine D2-like receptors

Abstract

Dopamine receptors are significantly involved in hippocampus-based cognitive processes. Whereas the involvement of D1-like receptors in hippocampal plasticity has been described, the role of D2-like receptors remains to be clarified. Therefore, we investigated the contribution of D2-like receptors to synaptic transmission, long-term potentiation (LTP) and depotentiation in the dentate gyrus of freely moving rats. Male Wistar rats underwent chronic implantation of a recording electrode in the granule cell layer, a stimulating electrode in the medial perforant path and a cannula in the ipsilateral cerebral ventricle (to enable drug administration). The D2-like receptor agonists quinpirole and noraporphine dose-dependently inhibited basal synaptic transmission. Agonist priming of D2-like receptors with a drug concentration which had no effect on synaptic transmission inhibited depotentiation but did not affect LTP. The agonist effects on depotentiation were prevented by the D2-like antagonist remoxipride. Remoxipride itself did not influence basal synaptic transmission or depotentiation. Interestingly, 'weak' LTP (<4 h) but not 'strong' LTP (>24 h) was inhibited by prior application of remoxipride. These results suggest a specific role for dopamine D2-like receptors in the regulation of both depotentiation and LTP in vivo and offer an important and novel insight as to the involvement of these receptors in processes related to learning and memory.