Ejaculation Induced by the Activation of Crz Neurons Is Rewarding to Drosophila Males

Abstract

The reward system is a collection of circuits that reinforce behaviors necessary for survival [1Kelley A.E. Berridge K.C. The neuroscience of natural rewards: relevance to addictive drugs.J. Neurosci. 2002; 22: 3306-3311Crossref PubMed Google Scholar, 2Edwards S. Koob G.F. Neurobiology of dysregulated motivational systems in drug addiction.Future Neurol. 2010; 5: 393-401Crossref PubMed Scopus (115) Google Scholar]. Given the importance of reproduction for survival, actions that promote successful mating induce pleasurable feeling and are positively reinforced [3Tenk C.M. Wilson H. Zhang Q. Pitchers K.K. Coolen L.M. Sexual reward in male rats: effects of sexual experience on conditioned place preferences associated with ejaculation and intromissions.Horm. Behav. 2009; 55: 93-97Crossref PubMed Scopus (100) Google Scholar, 4Paredes R.G. Evaluating the neurobiology of sexual reward.ILAR J. 2009; 50: 15-27Crossref PubMed Scopus (72) Google Scholar]. This principle is conserved in Drosophila, where successful copulation is naturally rewarding to male flies, induces long-term appetitive memories [5Shohat-Ophir G. Kaun K.R. Azanchi R. Mohammed H. Heberlein U. Sexual deprivation increases ethanol intake in Drosophila.Science. 2012; 335: 1351-1355Crossref PubMed Scopus (137) Google Scholar], increases brain levels of neuropeptide F (NPF, the fly homolog of neuropeptide Y), and prevents ethanol, known otherwise as rewarding to flies [6Devineni A.V. Heberlein U. Preferential ethanol consumption in Drosophila models features of addiction.Curr. Biol. 2009; 19: 2126-2132Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar, 7Kaun K.R. Azanchi R. Maung Z. Hirsh J. Heberlein U. A Drosophila model for alcohol reward.Nat. Neurosci. 2011; 14: 612-619Crossref PubMed Scopus (161) Google Scholar], from being rewarding [5Shohat-Ophir G. Kaun K.R. Azanchi R. Mohammed H. Heberlein U. Sexual deprivation increases ethanol intake in Drosophila.Science. 2012; 335: 1351-1355Crossref PubMed Scopus (137) Google Scholar]. It is not clear which of the multiple sensory and motor responses performed during mating induces perception of reward. Sexual interactions with female flies that do not reach copulation are not sufficient to reduce ethanol consumption [5Shohat-Ophir G. Kaun K.R. Azanchi R. Mohammed H. Heberlein U. Sexual deprivation increases ethanol intake in Drosophila.Science. 2012; 335: 1351-1355Crossref PubMed Scopus (137) Google Scholar], suggesting that only successful mating encounters are rewarding. Here, we uncoupled the initial steps of mating from its final steps and tested the ability of ejaculation to mimic the rewarding value of full copulation. We induced ejaculation by activating neurons that express the neuropeptide corazonin (CRZ) [8Tayler T.D. Pacheco D.A. Hergarden A.C. Murthy M. Anderson D.J. A neuropeptide circuit that coordinates sperm transfer and copulation duration in Drosophila.Proc. Natl. Acad. Sci. USA. 2012; 109: 20697-20702Crossref PubMed Scopus (89) Google Scholar] and subsequently measured different aspects of reward. We show that activating Crz-expressing neurons is rewarding to male flies, as they choose to reside in a zone that triggers optogenetic stimulation of Crz neurons and display conditioned preference for an odor paired with the activation. Reminiscent of successful mating, repeated activation of Crz neurons increases npf levels and reduces ethanol consumption. Our results demonstrate that ejaculation stimulated by Crz/Crz-receptor signaling serves as an essential part of the mating reward mechanism in Drosophila.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI1NWRhYzVmMDMwZWIwNDU2OWM5OTdlYzJiOTUxZTUwMiIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc3NjYyMDI0fQ.lFluPLjQVsI4e5rYXsW9-6Hkaqs6RW18ZWu5YE2N7VoE4_5VL8AU_02Vlt4MNyJj0QAdQ2NAJLXpg7xiVS21WpQQMCxaHCSBf6lW-u9JH5HRqIki8Swsv9E3K2IFuKeUJV5-7Ucl7LVK8PprVg_m96mjTqEuMaXsyGQ763gyThI1hIH-S5VrI3SuMhgL4ccRXHrzQQ8KKO-o4MAPnIGog2ovHWWEQGkJ2zl8ClYivjWlWb_lgCeet-As0wI4t5B0q-67CBXcGTNg9li7wetzLcO-WskS_k7ctk7tQ2wp-94MXBP7UsYwwRxbUxQrGhhRyA3eRIVxUkeyXvYc5EPtvA(mp4, (34.5 MB) Download video