Upregulation of nAChRs and Changes in Excitability on VTA Dopamine and GABA Neurons Correlates to Changes in Nicotine-Reward-Related Behavior.
Previous reports indicate that nicotine reward is mediated through α4β2*, α6β2*, and α4α6β2* nicotinic acetylcholine receptors (nAChRs; * indicates that additional nAChR subunits may be present). Little is known about α4α6β2* nAChR involvement in reward and reinforcement because of a lack of methods that allow the direct investigation of this particular nAChR subtype. Here, we use male and female mice that contain α4-mCherry and α6-GFP nAChR subunits to show that concentrations of nicotine sufficient to evoke reward-related behavior robustly upregulate α4* and α4α6* nAChRs on midbrain dopamine (DA) and GABA neurons. Furthermore, the extent of α4α6* nAChR upregulation on ventral tegmental area (VTA) DA neurons aligns with the magnitude of nicotine reward-related behavior. We also show that the upregulation of nAChRs is accompanied by a functional change in firing frequency of both DA and GABA neurons in the VTA that is directly linked to nicotine reward-related behavior.
['Akers|Austin T|AT|', 'Cooper|Skylar Y|SY|0000-0003-0646-6488', 'Baumgard|Zachary J|ZJ|', 'Casinelli|Gabriella P|GP|', 'Avelar|Alicia J|AJ|', 'Henderson|Brandon J|BJ|0000-0003-0381-028X']
D000818:Animals D004298:Dopamine D005260:Female D059330:GABAergic Neurons D008297:Male D051379:Mice D009538:Nicotine D011978:Receptors, Nicotinic D012201:Reward D015854:Up-Regulation D017557:Ventral Tegmental Area
upregulation excitability nicotine reward nicotinic receptor