title: Intracerebroventricular administration of ouabain alters synaptic plasticity and dopamine release in rat medial prefrontal cortex.
abstract: Intracerebroventricular (ICV) administration of ouabain, a specific Na-K-ATPase inhibitor, in rats mimics the manic phenotypes of bipolar disorder and thus has been proposed as one of the best animal models of mania. Bipolar mania has been known to be associated with dysfunctions of medial prefrontal cortex (mPFC), a brain area critically involved in mental functions; however, the exact mechanism underlying these dysfunctions is not yet clear. The present study investigated synaptic transmission, synaptic plasticity, and dopamine release in Sprague-Dawley rat mPFC following ICV administration of ouabain (5 μl of 1 mM ouabain). The electrophysiological results demonstrated that ouabain depressed the short- and the long-term synaptic plasticity, represented by paired-pulse facilitation and long-term potentiation, respectively, in the mPFC. These ouabain-induced alterations in synaptic plasticity can be prevented by pre-treatment with lithium (intraperitoneal injection of 47.5 mg/kg lithium, twice a day, 7 days), which acts as an effective mood stabilizer in preventing mania. The electrochemical results demonstrated that ICV administration of ouabain enhanced dopamine release in the mPFC, which did not be affected by pre-treatment with lithium. These findings suggested that alterations in synaptic plasticity and dopamine release in the mPFC might underlie the dysfunctions of mPFC accompanied with ouabain administration-induced bipolar mania.
authors: School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, 516 Jun Gong Road, Shanghai, 200093, China. lsui@usst.edu.cn
authors: Li
authors: L
authors: Sui
authors: Xiao-Jin
authors: XJ
authors: Song
authors: Jie
authors: J
authors: Ren
authors: Li-Hua
authors: LH
authors: Ju
authors: Yan
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D007276:Injections, Intraventricular; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D010042:Ouabain / Q000008:administration & dosage* / Q000633:toxicity; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D010042:Ouabain; D004298:Dopamine