Antagonism of dorsohippocampal orexin-2 receptors suppresses drug-seeking behavior: A neuropsychopharmacological study

[Speaker] Sadeghi, Bahman:1
1:Shahid Beheshti University of Medical Sciences, Department of Physiology, School of Allied medical Sciences (Iran)

Orexinergic system is engaged in reward circuitry and drug addiction. Here, effect of intrahippocampal CA1 administration of orexin-2 receptor (OX2r) antagonist, TCSOX229, on the acquisition and extinction of morphine conditioned place preference (CPP) was investigated in rats. CPP was induced by subcutaneous morphine injection during conditioning and TCSOX229 was bilaterally microinjected into the CA1. Conditioning scores and locomotor activities were recorded. Administration of the antagonist dose-dependently attenuates the induction of morphine CPP during acquisition while TCSOX229 did not have any influence on locomotor activity of all phases. At higher concentrations, TCSOX229 facilitated extinction of morphine CPP and decreased extinction latency period. OX2rs in the CA1 are involved in development of the acquisition and play a role in the extinction of morphine-seeking behavior. Blockade of OX2rs facilitates extinction and extinguishes the ability of drug-related cues, implicating that the antagonist might be considered as a propitious therapeutic agent in suppressing drug-seeking behavior.
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