title: Orexin-1 receptor signalling in the prelimbic cortex and ventral tegmental area regulates cue-induced reinstatement of ethanol-seeking in iP rats.
abstract: Orexins (hypocretins) are hypothalamic neuropeptides that innervate the entire neuraxis, including the prelimbic cortex and ventral tegmental area and have been implicated in ethanol-seeking behaviour. The present study aimed to use the orexin-1 (OX1 ) receptor antagonist SB-334867 to examine the role of prelimbic cortex and ventral tegmental area OX1 receptors in cue-induced reinstatement of ethanol-seeking. Ethanol-preferring rats (iP) rats were trained to self-administer ethanol (10 percent v/v, FR3) or sucrose (0.2-1 percent w/v, FR3) in the presence of reward-associated cues before being implanted with indwelling guide cannulae. Rats then underwent extinction training for 11 days. On test days, rats were given a microinjection of vehicle or SB-334867 (3 μg/side) and presented with reward-associated cues to precipitate reinstatement. Results show SB-334867 infused into the prelimbic cortex attenuated cue-induced reinstatement of ethanol-seeking, but not sucrose-seeking. OX1 antagonism in the ventral tegmental area also attenuated cue-induced reinstatement of ethanol-seeking. These findings suggest that OX1 receptors located in the prelimbic cortex and ventral tegmental area are part of a circuit driving cue-mediated ethanol-seeking behaviour.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia.
authors.forename: Robyn Mary
authors.initials: RM
authors.lastname: Brown
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia.|Departamento de Psicobiologia, Universidade Federal de São Paulo, Brazil.
authors.forename: Andrezza K
authors.initials: AK
authors.lastname: Kim
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia.|School of Psychology, University of New South Wales, Australia.
authors.forename: Shaun Yon-Seng
authors.initials: SY
authors.lastname: Khoo
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia.|Experimental Psychology, University of Cambridge, UK.
authors.forename: Bianca
authors.initials: B
authors.lastname: Jupp
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia.
authors.forename: Andrew John
authors.initials: AJ
authors.lastname: Lawrence
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001583:Benzoxazoles / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003213:Conditioning, Psychological; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D005108:Extinction, Psychological; D065726:Limbic Lobe / Q000378:metabolism; D008297:Male; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology; D064446:Orexin Receptors / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D002492:Central Nervous System Depressants; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000431:Ethanol; D014508:Urea
keywords: Cue-induced reinstatement; SB-334867; ethanol; orexin; prelimbic cortex; ventral tegmental area