Phasic Stimulation of Midbrain Dopamine Neuron Activity Reduces Salt Consumption

Abstract Salt intake is an essential dietary requirement, but excessive consumption is implicated in hypertension and associated conditions. Little is known about the neural circuit mechanisms that control motivation to consume salt, although the midbrain dopamine system, which plays a key role in other reward-related behaviours, has been implicated. We, therefore, examined the effects on salt consumption of either optogenetic excitation or chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons in male mice. Strikingly, optogenetic excitation of dopamine neurons decreased salt intake in a rapid and reversible manner, despite a strong salt appetite. Importantly, optogenetic excitation was not aversive, did not induce hyperactivity, and did not alter salt concentration preferences in a need-free state. In addition, we found that chemogenetic inhibition of dopamine neurons had no effect on salt intake. Lastly, optogenetic excitation of dopamine neurons reduced consumption of sucrose following an overnight fast, suggesting a more general role of VTA dopamine neuron excitation in organising motivated behaviors. Significance Statement Although it is well-established that midbrain dopamine neurons are involved in many types of reward-related behaviours, little is known about their role in salt intake under conditions where salt is appetitive (i.e. during salt depletion). Here, we show that optogenetic excitation of midbrain dopamine neurons can decrease salt intake. Importantly, this stimulation protocol did not affect salt concentration preferences. Furthermore, we find that this stimulation protocol can also reduce sucrose intake following an overnight fast, suggesting a broader role for dopamine neuron activity in regulating nutrient intake, which compliments findings from previous lesion- and pharmacological-based studies.