Across the animal kingdom, dopamine plays a crucial role in conferring reinforcement signals that teach animals about the causal structure of the world. In the fruit fly Drosophila melanogaster, the dopamine system has largely been studied using a rich genetic toolbox. Here, we suggest a complementary pharmacological approach applying the dopamine-synthesis inhibitor 3-Iodo-L-tyrosine (3IY), which causes acute systemic inhibition of dopamine signaling. Using Pavlovian conditioning, across developmental stages (3rd instar larva versus adult), valence domains (reward versus punishment), and types of reinforcement (natural versus optogenetically induced), we find that 3IY feeding specifically impairs associative learning, whereas additional feeding of L-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of dopamine, rescues this impairment. This study establishes a simple, quick, and comparably low-cost approach that can be combined with the available genetic tools to manipulate and clarify the functions of the dopaminergic system - in D. melanogaster and other animals.

Across the animal kingdom, dopamine plays a crucial role in conferring reinforcement signals that teach animals about the causal structure of the world. In the fruit fly Drosophila melanogaster, dopaminergic reinforcement has largely been studied using genetics, whereas pharmacological approaches have received less attention. Here, we apply the dopamine-synthesis inhibitor 3-Iodo-L-tyrosine (3IY), which causes acute systemic inhibition of dopamine signaling, and investigate its effects on Pavlovian conditioning. We find that 3IY feeding impairs sugar reward learning in larvae while leaving task-relevant behavioral faculties intact, and that additional feeding of a precursor of dopamine (L-3,4-dihydroxyphenylalanine, L-DOPA), rescues this impairment. Concerning a different developmental stage and for the aversive valence domain, we furthermore demonstrate that punishment learning by activating the dopaminergic neuron PPL1-γ1pedc in adult flies is also impaired by 3IY feeding and can likewise be rescued by L-DOPA. Our findings exemplify the advantages of using a pharmacological approach in combination with the genetic techniques available in D. melanogaster to manipulate neuronal and behavioral function.

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