NMDA receptors in the midbrain play a critical role in dopamine‐mediated hippocampal synaptic potentiation caused by morphine

Abstract A single exposure to drugs of abuse produces an NMDAR ( N ‐methyl‐ D ‐aspartate receptor)‐dependent synaptic potentiation at excitatory synapses of dopamine ( DA ) neurons in the ventral tegmental area ( VTA ) of the midbrain. All addictive drugs can increase DA concentrations in projection areas of the midbrain, including the hippocampus. Hippocampal DA release subsequently modulates hippocampal plasticity and drug‐associated memories. Using in vivo electrophysiological recording techniques in anesthetized rats, we show that systemic injection of morphine induced hippocampal synaptic potentiation in a dose‐dependent manner. Intra‐ VTA but not intra‐hippocampus injection of morphine evoked this potentiation. Local hippocampal dopamine D1 receptors ( D1R ) are required in the morphine‐induced synaptic potentiation and conditioned place preference ( CPP ). Moreover, both NMDAR activation in the VTA and VTA /hippocampus dopaminergic connections are essential for the morphine‐evoked potentiation and CPP . These findings suggest that NMDAR signalings in the midbrain play a key role in regulating dopamine‐mediated hippocampal synaptic plasticity underlying drug‐induced associative memory.