Exposure Of Nicotine To Ventral Tegmental Area Slices Induces Glutamatergic Synaptic Plasticity On Dopamine Neurons
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 Î±7-nAChR antagonist, methyllycaconitine (MLA) but not 1 Î¼M Î±4-containing nAChR antagonist, dihydro-Î²-erythroidine (DHÎ²E) prevents nicotinic effect, suggesting that Î±7-nAChRs are mainly mediated this nicotinic effect. This finding is further supported by the disappearance of this nicotinic effect in nAChR Î±7 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 Î±7 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 Î±7-nAChRs likely mediate this nicotinic effect through increasing presynaptic release of glutamate. Synapse, 2011. Â© 2010 Wiley-Liss, Inc.
Digital Object Identifier (DOI)
Jin, Yu; Yang, Kechun; Wang, Hong; and Wu, Jie, "Exposure Of Nicotine To Ventral Tegmental Area Slices Induces Glutamatergic Synaptic Plasticity On Dopamine Neurons" (2011). Neurobiology. 422.