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ABSTRACT PurposeAmphetamine (AMPH) increases locomotor activities in animals, and the locomotor response to AMPH is further modulated by caloric deficits such as food deprivation and restriction. The increment in locomotor activity regulated by AMPH‐caloric deficit concomitance can be further modulated by varying feeding schedules (e.g., acute and chronic food deprivation and acute feeding after chronic food deprivation). However, the effects of different feeding schedules on AMPH‐induced locomotor activity are yet to be explicated. Here, we have explored the stimulatory responses of acutely administered D‐amphetamine in locomotion under systematically varying feeding states (fed/sated and food deprivation) and schedules (chronic and acute) in zebrafish larvae. MethodWe exposed wild‐type and transgenic [Tg(mnx1:GCaMP5)] zebrafish larvae to 0.7 µM concentration of AMPH and measured swimming activity and spinal motor neuron activity in vivo in real time. The analysis involved time‐elapsed and cumulative manner pre‐ and post‐AMPH treatment in four different caloric states including acute and chronic schedules of feeding and hunger. Both locomotor and motor neuron activities were compared in all four states in both fish lines. FindingsOur results show that locomotion and motor neuron activity increased in both chronic and acute food deprivation post‐AMPH treatment cumulatively. A steady increase in locomotion was observed in acute food deprivation compared to an immediate abrupt increase in chronic food‐deprivation state. The ad libitum‐fed larvae exhibited a moderate increase both in locomotion and motor neuron activity. Conversely to all other caloric states, food‐sated (acute feeding after chronic food deprivation) larvae moved moderately less and exhibited a mild decrease in motor neuron activity after AMPH treatment. ConclusionThese results reveal the importance of cohesive effects of feeding schedule and AMPH treatment by revealing the changes in stimulatory characteristics of AMPH on locomotion and motor neuron activity in acute and chronic feeding states. 

ABSTRACT Dopamine (DA) signaling is evoked by both food and drugs that humans come to abuse. Moreover, physiological state (e.g., hunger versus satiety) can modulate the response. However, there is great heterogeneity among DA neurons. Limited studies have been performed that could resolve the interaction between physiological state and drug responsivity across groups of DA neurons. Here, we measured the activity of neurons in transgenic Tg (th2:GCaMP7s) zebrafish larva that expresses a calcium indicator (GCaMP7s) in A11 (posterior tuberculum) and a part of A14 (caudal hypothalamus and intermediate hypothalamus) DA populations located in the hypothalamus of the larval zebrafish. Fish were recorded in one of two physiological states: ad‐libitum fed (AL) and food deprived (FD) and before and after acute exposure to different doses of the stimulant drug amphetamine (0, 0.7, and 1.5 μM). We quantified fluorescence change, activity duration, peak rise/fall time, and latency in the calcium spikes of the DA neurons. Our results show that baseline DA neuron activity amplitude, spike duration, and correlation between inter‐ and intra‐DA neurons were higher in the FD than in the AL state. Dose‐dependent AMPH treatment further increased the intensity of these parameters in the neuron spikes but only in the FD state. The DA activity correlation relatively increased in AL state post‐AMPH treatment. Given that hunger increases drug reactivity and the probability of relapse to drug seeking, the results support populations of DA neurons as potential critical mediators of the interaction between physiological state and drug reinforcement.