Sexual Deprivation Increases Ethanol Intake in Drosophila

Abstract

The brain's reward systems evolved to reinforce behaviors required for species survival, including sex, food consumption, and social interaction. Drugs of abuse co-opt these neural pathways, which can lead to addiction. Here, we use Drosophila melanogaster to investigate the relationship between natural and drug rewards. In males, mating increased Neuropeptide F (NPF) levels, whereas sexual deprivation reduced NPF. Activation or inhibition of the NPF system in turn enhanced or reduced ethanol preference. These results thus link sexual experience, NPF system activity, and ethanol consumption. Artificial activation of NPF neurons was in itself rewarding and precluded the ability of ethanol to act as a reward. We propose that activity of the NPF/NPF receptor axis represents the state of the fly reward system and modifies behavior accordingly.

Dissection of theDrosophilaneuropeptide F circuit using a high-throughput two-choice assay

“…In addition, NPY neurons in the central nucleus of the amygdala and the arcuate nucleus of the hypothalamus send projections to the nucleus accumbens (37), and intraaccumbens injections of NPY are able to produce a place preference response in rats (38). Similarly, the fly NPF neurons regulate several reward related behaviors, such as retrieval of appetitive memories (22), and alcohol preference and reward (10). In addition, thermogenetic activation of these neurons is per se rewarding (10).…”

“…Before doing so, we analyzed in detail the expression pattern of NPF-GAL4 driving expression of 20XUAS-mCD8-GFP (NPF>GFP). The NPF-GAL4 transgene used here has been described previously to mimic faithfully the endogenous NPF expression pattern (10,19). The pattern includes two sets of large neurons named L1-l and P1 (ref.…”

“…It has also been shown that thermogenetic activation of NPF neurons can mimic the effect of starvation by gating the retrieval of appetitive olfactory memories (22). In addition, activation of NPF cells was able to reduce the rewarding effects of ethanol and was shown to be intrinsically rewarding (10). Moreover, it has been proposed that state of the fly reward system is regulated by the activity of NPF neurons (10).…”

“…In addition, activation of NPF cells was able to reduce the rewarding effects of ethanol and was shown to be intrinsically rewarding (10). Moreover, it has been proposed that state of the fly reward system is regulated by the activity of NPF neurons (10).…”

Peptidomics of Neuropeptidergic Tissues of the Tsetse FlyGlossina morsitans morsitans

“…Like its mammalian counterpart neuropeptide Y, NPF is primarily known for its role in feeding behavior [86], but is also involved in several other behavioral processes including mating behavior-associated activity [87][88][89], sleep [90], aggression [91], and ethanol sensitivity [92]. Dipteran NPF expression is observed in larval and adult brain tissue and endocrine cells in the midgut [93,94].…”