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

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. [ABSTRACT FROM AUTHOR]