Role of Orexin-1 Receptor Within the Ventral Tegmental Area in Mediating Stress- and Morphine Priming-induced Reinstatement of Conditioned Place Preference in Rats

Orexin-containing neurons exist in the lateral hypothalamic region, sending their projections toward mesolimbic regions such as the Ventral Tegmental Area (VTA).


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 “off” 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 µL 12% DMSO per side) and bilaterally were subsequently tested for FSS- and morphine priming-induced reinstatement.


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.


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.

Article Type:
Research/Original Article
Basic and Clinical Neuroscience, Volume:10 Issue:4, 2019
373 - 382  
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