Mechanisms Involved In Systemic Nicotine-Induced Glutamatergic Synaptic Plasticity On Dopamine Neurons In The Ventral Tegmental Area
Systemic exposure to nicotine induces glutamatergic synaptic plasticity on dopamine (DA) neurons in the ventral tegmental area (VTA), but mechanisms are largely unknown. Here, we report that single, systemic exposure in rats to nicotine (0.17 mg/kg free base) increases the ratio of DA neuronal currents mediated by AMPA relative to NMDA receptors (AMPA/NMDA ratio) assessed 24 h later, based on slice-patch recording. The AMPA/NMDA ratio increase is evident within 1 h and lasts for at least 72 h after nicotine exposure (and up to 8 d after repeated nicotine administration). This effect cannot be prevented by systemic injection of either Î±7-nAChR (nicotinic ACh receptor)-selective [methyllycaconitine (MLA)] or Î²2*-nAChR-selective [mecamylamine (MEC)] antagonists but is prevented by coinjection of MLA and MEC. In either nAChR Î±7 or Î²2 subunit knock-out mice, systemic exposure to nicotine still increases the AMPA/NMDA ratio. Preinjection in rats of a NMDA receptor antagonist MK-801((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10- imine maleate), but neither DA receptor antagonists [SCH-23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) plus haloperidol] nor a calcineurin inhibitor (cyclosporine), prevents the nicotine-induced increase in AMPA/NMDA ratio. After systemic exposure to nicotine, glutamatergic (but not GABAergic) transmission onto rat VTA DA neuronal inputs is enhanced. Correspondingly, DA neuronal firing measured 24 h after nicotine exposure using extracellular single-unit recording in vivo is significantly faster, and there is conversion of silent to active DA neurons. Collectively, these findings demonstrate that systemic nicotine acting via either Î±7- or Î²2*-nAChRs increases presynaptic and postsynaptic glutamatergic function, and consequently initiates glutamatergic synaptic plasticity, which may be an important, early neuronal adaptation in nicotine reward and reinforcement. Copyright Â© 2010 the authors.
Journal of Neuroscience
Digital Object Identifier (DOI)
Gao, Ming; Jin, Yu; Yang, Kechun; Zhang, Die; Lukas, Ronald J.; and Wu, Jie, "Mechanisms Involved In Systemic Nicotine-Induced Glutamatergic Synaptic Plasticity On Dopamine Neurons In The Ventral Tegmental Area" (2010). Translational Neuroscience. 246.