Modulation of Hypothalamic Dopamine Neuron Activity by Interaction Between Caloric State and Amphetamine in Zebrafish Larvae.

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.