Dopamine-induced synaptic plasticity in the amygdala in saline-and cocaine-treated animals undergoing conditioned place preference
Kathy Marie Genzer
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One of the biggest problems facing cocaine addicts is relapse and currently there are no treatments for relapse. These studies will provide insight into the underlying mechanisms of LTP mediating relapse to cocaine. A major mechanism of cocaine in addiction is to inhibit dopamine re-uptake and glutamate is an excitatory neurotransmitter involved in addiction. Previous studies have demonstrated a link between phospholipase D (PLD) and metabotropic glutamate receptors (mGluRs), while other studies show an interaction between dopamine receptors (DRs) and PLD. Therefore, we investigated the mechanisms of the dopamine agonist-induced synaptic plasticity that is enhanced in the amygdala due to cocaine exposure in the Central-Basolateral Amygdala (CeA-BLA) pathway. Electrophysiology recordings showed that the dopamine agonist-induced LTP is mediated via D1 receptors and is dependent upon mGluR1 and the mGluR linked to PLD and partially dependent upon mGluR5 and phospholipase C (PLC). Western blots and co-immunoprecipitations revealed increased expression of PLD after cocaine administration and possible physical interactions between group I mGluRs and PLD and DRs and PLD. PLD activity assays showed that PLD activity was decreased by antagonists of mGluR1 and the mGluR linked to PLD and was increased by the agonist for the mGluR linked to PLD. Basal PLD activity may also be mediated by D1 receptors and was not affected by mGluR5 antagonists.