Involvement of orexin receptors within the hippocampal dentate gyrus in morphine-induced reinstatement in food-deprived rats

•Blockade of orexin-2 receptors in the DG considerably decreased the morphine-induced reinstatement in the food-deprived rats.•High dose of intra-DG SB334867 could decrease the reinstatement induced by FD and sub-threshold dose of morphine.•The contribution of OX2Rs in the DG to stress-induced reins...

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Published in:Behavioural brain research 2019-12, Vol.375, p.112155-112155, Article 112155
Main Authors: Pourhamzeh, Mahsa, Mozafari, Roghaye, Jamali, Shole, Motamedi, Fereshteh, Ahadi, Reza, Haghparast, Abbas
Format: Article
Language:English
Subjects:
Conditioned place preference
Dentate gyrus
Food deprivation
Morphine
Orexin receptor
Rat
Reinstatement
Reward
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Summary:•Blockade of orexin-2 receptors in the DG considerably decreased the morphine-induced reinstatement in the food-deprived rats.•High dose of intra-DG SB334867 could decrease the reinstatement induced by FD and sub-threshold dose of morphine.•The contribution of OX2Rs in the DG to stress-induced reinstatement was more than OX1Rs in extinguished morphine-induced CPP. The orexinergic system is found to cooperate in mediating stress-induced drug relapse. The orexinergic terminals innervate neurons of the hippocampal dentate gyrus (DG) which is a key structure in the maintenance and reinstatement of drug addiction. However, the specific contribution of intra-DG orexin receptors to stress-induced reinstatement has not been completely known. In the current study, the effects of intra-DG administration of SB334867, an orexin-1 receptor (OX1R) antagonist, and TCS OX2 29, an orexin-2 receptor (OX2R) antagonist, were investigated on the reinstatement induced by a sub-threshold dose of morphine and food deprivation (FD) stress. Adult male rats received different doses of SB334867 or TCS OX2 29 (3, 10, and 30 nM/0.5 μl DMSO 12%) bilaterally into the DG in separate groups, following the acquisition and extinction of morphine-induced conditioned place preference (CPP). Then, the reinstatement was evaluated by the 24 h FD stress and/or a sub-threshold dose of morphine (0.5 mg/kg, s.c.). CPP scores and locomotor activities were recorded during the test. The findings indicated that pre-treatment with the highest dose of SB334867 (30 nM) and two higher doses of TCS OX2 29 (10 and 30 nM) blocked the sub-threshold dose and FD stress-induced reinstatement of morphine. The effect of TCS OX2 29 on reduction of reinstatement was more pronounced than that of SB334867. It suggests a role for the orexin receptors, especially OX2R within the DG region in the stress-induced reinstatement of morphine-seeking behaviours in extinguished rats.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2019.112155