Come Fly with Me: An overview of dopamine receptors in Drosophila melanogaster

Abstract

Dopamine (DA) receptors play critical roles in a wide range of behaviours, including sensory processing, motor function, reward and arousal. As such, aberrant DA signalling is associated with numerous neurological and psychiatric disorders. Therefore, understanding the mechanisms by which DA neurotransmission drives intracellular signalling pathways that modulate behaviour can provide critical insights to guide the development of targeted therapeutics. Drosophila melanogaster has emerged as a powerful model with unique advantages to study the mechanisms underlying DA neurotransmission and associated behaviours in a controlled and systematic manner. Many regions in the fly brain innervated by dopaminergic neurons have been mapped and linked to specific behaviours, including associative learning and arousal. Here, we provide an overview of the homology between human and Drosophila dopaminergic systems and review the current literature on the pharmacology, molecular signalling mechanisms and behavioural outcome of DA receptor activation in the Drosophila brain.

Receptors and Channels Associated with Alcohol Use: Contributions from Drosophila

“…Dop2R shows 46% amino acid sequence similarity to human DRD2. 22 For an extensive discussion of dopamine receptor homology, pharmacology, and signaling mechanisms see Karam et al 69 …”

The Neurotransmitters Involved in Drosophila Alcohol-Induced Behaviors

“…The D2-like receptor, Dop2R, inhibits the adenylyl cyclase/cAMP pathway (Scholz-Kornehl and Schwärzel, 2016). Both classes are G proteincoupled receptors (GPCRs) with seven transmembrane domains (Karam et al, 2020). Flies also have DopEcR, a G protein-coupled DA/ecdysteroid receptor that can be activated by either DA or the insect hormone ecdysone (Srivastava et al, 2005).…”

“…Flies also have DopEcR, a G protein-coupled DA/ecdysteroid receptor that can be activated by either DA or the insect hormone ecdysone (Srivastava et al, 2005). Much of the structure of these receptors is conserved between vertebrates and Drosophila (Karam et al, 2020). After the presynaptic neuron releases DA into the synapse and DAergic action occurs, the dopamine transporter (DAT) takes DA back up into the neuron.…”

Associative learning in larval and adult Drosophila is impaired by the dopamine-synthesis inhibitor 3-Iodo-L-tyrosine

“…The genetic tools available for D. melanogaster allowed the genetic and neuronal mechanisms of learning and memory to be investigated, and revealed many striking similarities between the dopaminergic systems of flies and mammals, including humans (reviewed in Yamamoto and Seto, 2014). To mention but a few, flies and mammals share most genes involved in dopamine synthesis, secretion and signaling (Clark et al, 1978;Karam et al, 2019;Riemensperger et al, 2011;Yamamoto and Seto, 2014), and they also have in common the crucial role of dopaminergic neurons in reinforcement signaling (Burke et al, 2012;Liu et al, 2012;Schroll et al, 2006;Schwaerzel et al, 2003;Selcho et al, 2009;reviewed in Scaplen and Kaun, 2016). Of note is that in D. melanogaster different sets of dopaminergic neurons signal appetitive or aversive reinforcement, respectively, to distinct compartments of the insects' memory center, the mushroom body, which harbors a sparse and specific representation of the olfactory environment (Diegelmann et al, 2013;Guven-Ozkan and Davis, 2014;Heisenberg, 2003;Owald and Waddell, 2015;Thum and Gerber, 2019).…”