title: 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.
authors.affiliation: Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Hu
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Jing
authors.forename: Cai-Lian
authors.initials: CL
authors.lastname: Cui
authors.forename: Guo-Gang
authors.initials: GG
authors.lastname: Xing
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D055366:Synaptic Potentials / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D015259:Dopamine Agents; D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine; D004298:Dopamine