Exposure of nicotine to ventral tegmental area slices induces glutamatergic synaptic plasticity on dopamine neurons

Yu Jin, Kechun Yang, Hong Wang, Jie Wu

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Nicotine promotes glutamatergic synaptic plasticity in dopaminergic (DA) neurons in the ventral tegmental area (VTA), which is thought to be an important mechanism underlying nicotine reward. However, it is unclear whether exposure of nicotine alone to VTA slice is sufficient to increase glutamatergic synaptic strength on DA neurons and which nicotinic acetylcholine receptor (nAChR) subtype mediates this effect. Here, we report that the incubation of rat VTA slices with 500 nM nicotine induces glutamatergic synaptic plasticity in DA neurons. We measure the ratio of AMPA and NMDA receptor-mediated currents (AMPA/NMDA) and compare these ratios between nicotine-treated and -untreated slices. Our results demonstrate that the incubation of VTA slices with 500 nM nicotine for 1 h (but not for 10 min) significantly increases the AMPA/NMDA ratio when compared with controls. Preincubation with 10 nM of the α7-nAChR antagonist, methyllycaconitine (MLA) but not 1 μM α4-containing nAChR antagonist, dihydro-β-erythroidine (DHβE) prevents nicotinic effect, suggesting that α7-nAChRs are mainly mediated this nicotinic effect. This finding is further supported by the disappearance of this nicotinic effect in nAChR α7 knockout (KO) mice. Furthermore, nicotine reduced paired-pulse ratio (PPR) of evoked excitatory postsynaptic potential (eEPSP) in the VTA slices prepared from wild-type (WT) mice but not α7 KO mice. Collectively, these findings suggest that exposure of smoking-relevant concentrations of nicotine to VTA slices is sufficient to increase glutamatergic synaptic strength on DA neurons and that α7-nAChRs likely mediate this nicotinic effect through increasing presynaptic release of glutamate. Synapse, 2011.

Original languageEnglish (US)
Pages (from-to)332-338
Number of pages7
JournalSynapse
Volume65
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

Keywords

  • Dopamine neuron
  • Glutamatergic synaptic plasticity
  • Nicotine
  • Nicotinic acetylcholine receptor
  • Patch clamp
  • Ventral tegmental area

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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