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The Journal of Neuroscience, 0000, 20:RC106:1-5

RAPID COMMUNICATION
Essential Role of D1 But Not D2 Receptors in the NMDA Receptor-Dependent Long-Term Potentiation at Hippocampal-Prefrontal Cortex Synapses In Vivo

Hirac Gurden¹, Masatoshi Takita², and Thérèse M. Jay¹

¹ Neurobiologie de l'Apprentissage, de la Mémoire et de la Communication, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8620, 91405 Orsay, France, and ² Neuroinformatics Laboratory, National Institute of Bioscience and Human Technology, Tsukuba, Ibaraki, 305-8566, Japan

An intact mesocortical dopaminergic (DA) input to the prefrontal cortex (PFC) has been reported to be necessary for long-term potentiation (LTP) to occur at hippocampal-prefrontal cortex synapses. Here, we investigated the role of D1 and D2 receptors in this NMDA receptor-dependent LTP. Local infusion of the D1 agonist SKF81297 at an optimal dose induced a sustained enhancement of hippocampal-PFC LTP, whereas the D1 antagonist SCH23390 caused a dose-related impairment of its induction. The D1 agonist effect was mimicked by infusion of a low dose of the adenylyl cyclase activator forskolin, whereas LTP was severely attenuated with a protein kinase A inhibitor, Rp-cAMPS. To further assess the complex interplay between DA and NMDA receptors, changes in extracellular DA levels in the PFC were estimated during LTP, and a significant increase was observed immediately after tetanus. Taken together, these data suggest that D1 but not D2 receptors are crucial for the DA control of the NMDA receptor-mediated synaptic response on a specific excitatory input to the PFC. The interactions of these receptors may play a crucial role in the storage and transfer of hippocampal information in the PFC.

Key words: prefrontal cortex; dopamine; synaptic plasticity; hippocampus; SCH23390; SKF81297; sulpiride; Rp-cAMPS; forskolin

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Copyright © 0000 Society for Neuroscience  0270-6474/00/$05.00/0

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