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| Paper IPM / Cognitive / 14551 |
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Locus coeruleus (LC), a pontine brainstem structure has been shown to be importantly involved in opiate dependency. LC neurons are innervated by dense hypothalamic fibers which contain two neuropeptides, Orexin and Dynorphin, coexpressed in the same synaptic vesicles. LC neurons express both kappaopioid (KORs) and orexin type 1 receptors (OX1Rs). The functional interaction between these two neuropeptides during addictive behaviors, including morphine place aversion, has not been well studied. Here, we examined the role of LC KORs and OX1Rs blockade, separately and together to investigate naloxoneinduced conditioned place aversion (CPA) of morphinedependent rats. In this study we used CPA in male Wistar rats, made them morphine dependent by subcutaneous injection of morphine sulfate (10 mg/kg) at an interval of 12 h for 9 days. On the conditioning days, naloxone (1 mg/kg, i.p.) was injected 2 h after morphine administration. IntraLC injection of NorBNI (KORs antagonist) and SB334867 (OX1R antagonist) prior to each conditioning session was used to assess the effect of blockade of these receptors. We found that disruption of orexin function in the LC reduced the expression of morphine CPA. Also our results showed that blockade of KORs, 24 h before conditioning session, reduced morphine CPA, while concomitant antagonism of OX1Rs and KORs abolishes this behavioral effect. These results reveal an interaction between dynorphin and orexin in the LC during conditioned place aversion. Blocking the dynorphin and orexin system within the LC separately reduces the negative emotional state of withdrawal which would be expected to reduce the probability of relapse. Identifying the mechanisms underlying the loss of the CPA effect in the presence of concomitant use of dynorphin and orexin receptor antagonists, needs further evaluations.
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