Mechanisms Underlying the Risk to Develop Drug Addiction, Insights From Studies in Drosophila melanogaster

Abstract

The ability to adapt to environmental changes is an essential feature of biological systems, achieved in animals by a coordinated crosstalk between neuronal and hormonal programs that allow rapid and integrated organismal responses. Reward systems play a key role in mediating this adaptation by reinforcing behaviors that enhance immediate survival, such as eating or drinking, or those that ensure long-term survival, such as sexual behavior or caring for offspring. Drugs of abuse co-opt neuronal and molecular pathways that mediate natural rewards, which under certain circumstances can lead to addiction. Many factors can contribute to the transition from drug use to drug addiction, highlighting the need to discover mechanisms underlying the progression from initial drug use to drug addiction. Since similar responses to natural and drug rewards are present in very different animals, it is likely that the central systems that process reward stimuli originated early in evolution, and that common ancient biological principles and genes are involved in these processes. Thus, the neurobiology of natural and drug rewards can be studied using simpler model organisms that have their systems stripped of some of the immense complexity that exists in mammalian brains. In this paper we review studies in Drosophila melanogaster that model different aspects of natural and drug rewards, with an emphasis on how motivational states shape the value of the rewarding experience, as an entry point to understanding the mechanisms that contribute to the vulnerability of drug addiction.

Differential dysregulation of CREB and synaptic genes in transgenic Drosophila melanogaster expressing shaggy (GSK3), TauWT, or Amyloid-beta

“…At last, to examine whether the change in CREB transcript level is through GSK3/CREB pathway, we spotted the expression of shaggy in Tau WT or Aβ 42 transgenic ies. The current study showed that ectopic expression of Tau WT in the drosophila nerve system upregulated transcription of shaggy, which is consistent with the nding of a preceding study demonstrating that mRNA level of GSK3β has been elevated in the hippocampus at the early stages of Alzheimer's disease [33]. However, we observed that Aβ 42 did not affect shaggy expression.…”

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

“…Dopamine signaling serves multiple functions, including movement initiation, sleep regulation, motivation, learning, memory extinction and forgetting (Berke, 2018;Meder et al, 2019;Oishi and Lazarus, 2017;Schultz, 2007;Yamamoto and Seto, 2014). In particular, it is crucial for conferring reinforcement signals that teach animals about the causal structure of the world (Ryvkin et al, 2018;Schultz, 2015;Waddell, 2013;Yamamoto and Vernier, 2011). This important role of dopamine is found across the animal kingdom, including the fruit fly Drosophila melanogaster.…”

Post-Developmental Roles of Notch Signaling in the Nervous System

“…Molecules that are associated with addiction such as recreational drugs, alcohol, and nicotine impinge on these neuromodulator pathways to alter behavior, and the underlying molecular pathway and mechanisms are highly conserved [ 72 , 73 , 74 ]. Over the past decade, geneticists have been using Drosophila to understand the molecular basis of addiction by using sophisticated genetic tools and specialized behavioral assays [ 75 , 76 , 77 ].…”