The role of orexin on GABAA receptor activity during morphine withdrawal syndrome in rat locus coeruleus neurons

The neuropeptide orexin is synthetized in the lateral hypothalamus (LH) and is involved in naloxone-precipitated morphine withdrawal syndrome via orexin type 1 receptors (OX1R). Locus coeruleus (LC) is a sensitive site for the expression of somatic aspects of morphine withdrawal. The orexinergic and GABA-A-ergic systems are involved in morphine withdrawal syndrome. In this study, the effect of OX1R at the LC neurones on GABA-A-ergic inhibitory system activity in morphine withdrawal syndrome was investigated.

Male Wistar rats (14-21 days) were made dependent on morphine (20 mg/kg, i.p., for 7 days). Then the effect of orexin-A on spontaneous and evoked inhibitory post synaptic currents in LC neurons using whole-cell patch clamp recordings was assessed.

The findings of this study indicated that orexin-A through OX1R in the presence of naloxone may induce an inhibitory effect on GABAergic system in the LC neurons. It seems that the orexin-A administration decreased the eIPSCs amplitude in LC neurons. OrexinA decreased spontaneous sIPSCs frequency of LC neurons, but did not change the sIPSCs amplitude in the presence of naloxone.

These findings implicated evidence that orexin-A via OX1R may participate in expression of naloxone-precipitated morphine withdrawal syndrome through decreasing of GABAA receptor activity.