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 (10percent v/v, FR3) or sucrose (0.2-1percent 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 (3g/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.National Health and Medical Research Council of AustraliaAustralian Research CouncilAustralian Postgraduate AwardBesen Family FoundationVictorian GovernmentUniv Melbourne, Florey Inst Neurosci & Mental Hlth, 30 Royal Parade, Parkville, Vic 3052, AustraliaUniv Fed Sao Paulo, Dept Psicobiol, Sao Paulo, BrazilUniv New S Wales, Sch Psychol, Sydney, NSW 2052, AustraliaUniv Cambridge, Expt Psychol, Cambridge CB2 1TN, EnglandUniv Fed Sao Paulo, Dept Psicobiol, Sao Paulo, BrazilNHMRCA: 1021227Web of Scienc
