Food deprivation modulates heart rate, motor neuron, and locomotion responses to acute administration of d-amphetamine in zebrafish larvae

Abstract

AbstractPsychostimulant drugs are so named because they alter the cardiac, brain and behavioral responses in humans and other animals. Acute food deprivation or chronic food restriction potentiates the stimulatory effects of abused drugs and increases the propensity for relapse to drug seeking in drug-experienced animals. The mechanisms by which hunger affects cardiac and behavioral activities are only beginning to be elucidated. Moreover, changes in motor neuron activities at the single neuron level induced by the stimulants, and their modulation by hunger, remain unknown. Here we investigated how the state of hunger affects responses to d-amphetamine by measuring locomotion, cardiac output, and individual motor neuron activity in zebrafish larvae. We used wild-type larval zebrafish to record behavioral and cardiac responses and the larvae of mnx1:GCaMP transgenic zebrafish to record motor neuron responses. Acute administration of d-amphetamine in sated larvae did not induce a significant change in the motor responses (swimming distances, tail activity), heart rate, or motor neuron firing frequency to the stimulant. However, food deprivation enhanced amphetamine-evoked responses significantly. The results extend the finding that signals arising from food deprivation are a key potentiator of the drug responses induced by d-amphetamine to the zebrafish model. The larval zebrafish is an ideal model to further elucidate this interaction and identify key neuronal substrates that may increase vulnerability to drug reinforcement, drug-seeking and relapse.