Direct and indirect interactions between cannabinoid CB1 receptor and group II metabotropic glutamate receptor signalling in layer V pyramidal neurons from the rat prefrontal cortex

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Abstract
At proximal synapses from layer V pyramidal neurons from the rat prefrontal cortex, activation of group II metabotropic glutamate receptors (group II mGlu) by (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl) glycine (DCG IV) induced a long‐lasting depression of excitatory postsynaptic currents. Paired‐pulse experiments suggested that the depression was expressed presynaptically. Activation of type 1 cannabinoid receptors (CB1) by WIN 55,212‐2 occluded the DCG IV‐induced depression in a mutually occlusive manner. At the postsynaptic level, WIN 55,212‐2 and DCG IV were also occlusive for the activation of extracellular signal‐regulated kinase. The postsynaptic localization of active extracellular signal‐regulated kinase was confirmed by immunocytochemistry after activation of CB1 receptors. However, phosphorylation of extracellular signal‐regulated kinase in layer V pyramidal neurons was dependent on the activation of N‐methyl‐d‐aspartate receptors, consequently to a release of glutamate in the local network. Group II mGlu were also shown to be involved in long‐term changes in synaptic plasticity induced by high frequency stimulations. The group II mGlu antagonist (RS)‐alpha‐methylserine‐O‐phosphate monophenyl ester (MSOPPE) favoured long‐term depression. However, no interaction was found between MSOPPE, WIN 55,212‐2 and the CB1 receptor antagonist SR 141716A on the modulation of long‐term depression or long‐term potentiation and the effects of these drugs were rather additive. We suggest that CB1 receptor and group II mGlu signalling may interact through a presynaptic mechanism in the induction of a DCG IV‐induced depression. Postsynaptically, an indirect interaction occurs for activation of extracellular signal‐regulated kinase. However, none of these interactions seem to play a role in synaptic plasticities induced with high frequency stimulations.