Sexual Deprivation Increases Ethanol Intake in Drosophila

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Abstract: The brain’s reward systems 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. 

In males, mating increased, whereas sexual deprivation reduced, neuropeptide F (NPF) levelsActivation or inhibition of the NPF system in turn reduced or enhanced ethanol preferenceThese 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.

Natural rewards and abused drugs affect the function of the brain’s reward systems, and abnormal function of these brain regions is associated with addictive

Thus, the effects of sexual deprivation can be reversed by copulation, which is consistent with sexual deprivation being the major contributor to ethanol preference.

We focused on Drosophila neuropeptide F (NPF) as a potential mediator of the effects of sexual experience.

The mammalian neuropeptide regulates ethanol consumption. Intriguingly, stressful experiences regulate mammalian NPY levels. These include restraint stress and early maternal separation in rodents and post-traumatic stress disorder in humans.

We propose that the activity of the NPF-NPFR system may be a neural representation of the state of the Drosophila reward system.  If so, experiences that change NPF-NPFR activity should promote behaviors that restore the system to its normal state.

In this model, sexual deprivation would create an NPF deficit that increases reward-seeking behavior such as ethanol consumption. Conversely, successful copulation would create a NPF surfeit that reduces reward seeking. This model predicts that mating and ethanol consumption should be rewarding, that activation of the NPF-NPFR pathway is rewarding per se, and that artificial activation of the NPF circuit will diminish ethanol reward-seeking behavior.

Regardless of the exact mechanism, these data suggest that activity of the NPF system is regulated by at least two rewarding experiences, mating and ethanol intoxication.

Mammalian NPY has several distinct behavioral functions that are mediated by different brain regions, including roles in feeding, anxiety, stress, sleep regulation, sexual motivation, and ethanol consumption.

Our findings are thus not only consistent with known functions of mammalian NPY and its mode of regulation, but also provide evidence for NPF functioning as a key molecular transducer between social experience and drug reward. Drosophila is a useful and accessible model system in which to decipher the mechanisms by which social experiences interact with reward systems.

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