title: The role of ghrelin signalling for sexual behaviour in male mice.
abstract: Ghrelin, a gut-brain signal, is well known to regulate energy homeostasis, food intake and appetite foremost via hypothalamic ghrelin receptors (GHS-R1A). In addition, ghrelin activates the reward systems in the brain, namely the mesolimbic dopamine system, and regulates thereby the rewarding properties of addictive drugs as well as of palatable foods. Given that the mesolimbic dopamine system mandates the reinforcing properties of addictive drugs and natural rewards, such as sexual behaviour, we hypothesize that ghrelin plays an important role for male sexual behaviour, a subject for the present studies. Herein we show that ghrelin treatment increases, whereas pharmacological suppression (using the GHSR-1A antagonist JMV2959) or genetic deletion of the GHS-R1A in male mice decreases the sexual motivation for as well as sexual behaviour with female mice in oestrus. Pre-treatment with L-dopa (a dopamine precursor) prior to treatment with JMV2959 significantly increased the preference for female mouse compared with vehicle treatment. On the contrary, treatment with 5-hydroxythyptohan (a precursor for serotonin) prior to treatment with JMV2959 decreased the sexual motivation compared to vehicle. In separate experiments, we show that ghrelin and GHS-R1A antagonism do not affect the time spent over female bedding as measured in the androgen-dependent bedding test. Collectively, these data show that the hunger hormone ghrelin and its receptor are required for normal sexual behaviour in male mice and that the effects of the ghrelin signalling system on sexual behaviour involve dopamine neurotransmission.
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Emil
authors.initials: E
authors.lastname: Egecioglu
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Luna
authors.initials: L
authors.lastname: Prieto-Garcia
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Studer
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Westberg
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Jerlhag
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002491:Central Nervous System Agents / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D054439:Ghrelin / Q000494:pharmacology / Q000502:physiology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D052586:Mating Preference, Animal / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009042:Motivation; D011930:Reaction Time; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors; D012726:Sexual Behavior, Animal / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D002491:Central Nervous System Agents; D015259:Dopamine Agents; D054439:Ghrelin; C569751:N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide; D054440:Receptors, Ghrelin; D014230:Triazoles; D007980:Levodopa; D006916:5-Hydroxytryptophan; D005998:Glycine
keywords: Addiction; appetite; dopamine; ghrelin; reward; sexual behaviour