en Behavioral Neuroscience Behavioral Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: Orexin-containing neurons exist in the lateral hypothalamic region, sending their projections toward mesolimbic regions such as the Ventral Tegmental Area (VTA).<br> <strong>Methods</strong>: In the current study, a Reinstatement model is used to examine the effects of intra-VTA administration of SB334867 as an Orexin-1 Receptor (OX1R) antagonist on drug priming- and Forced Swim Stress (FSS)-induced reinstatement of morphine. Eighty-eight male adult albino Wistar rats, weighing 200-280 g, were bilaterally implanted by cannulas into the VTA. We induced the Conditioned Place Preference (CPP) by Subcutaneous (SC) injection of morphine (5 mg/kg) daily in three days. Then, the CPP score was calculated. After a 24-h &ldquo;off&rdquo; period following achievement of extinction criterion, the rats were tested for drug priming-induced reinstatement by a priming dose of morphine (1 mg/kg, SC) and for FSS-induced reinstatement 10 min after FSS. In the next experiments, the animals received different doses of intra-VTA administration of SB334867 (0.3, 3, and 1 nM/0.3 &micro;L 12% DMSO per side) and bilaterally were subsequently tested for FSS- and morphine priming-induced reinstatement.<br> <strong>Results</strong>: Our findings indicated that the FSS could induce the reinstatement of seeking behaviors. Furthermore, intra-VTA administration of OX1R antagonists suppressed FSS- and drug priming-induced reinstatement dose-dependently.<br> <strong>Conclusion</strong>: It is concluded that FSS and drug priming-induced reinstatement might be mediated, at least in part, by stimulation of orexin receptors in the VTA.</div> Reward, Orexin system, Reinstatement, Ventral tegmental area, Forced swim stress, Conditioned place preference 373 382 http://bcn.iums.ac.ir/browse.php?a_code=A-10-1301-1&slc_lang=en&sid=1 Ronak Azizbeigi razizbeigi@yhoo.com; ronak.azizbeigi@iausdj.ac.ir 13700319475328460021094 13700319475328460021094 Yes Department of Physiology, Faculty of Veterinary Medicine, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran. Zahra Farzinpour 13700319475328460021095 13700319475328460021095 No CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China. Abbas Haghparast 13700319475328460021096 13700319475328460021096 No Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.