Physiology & Pharmacology
mahnaz davoudi; Hossein azizi; Javad Mirnajafi-Zadeh; saeed semnanian
Volume 27, Issue 5 , November and December 2020, , Pages 630-639
Abstract
Introduction: 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 ...
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Introduction: 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.
Materials and Methods: 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.
Results: 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.
Conclusion: 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.
Yousof Mousavi; Hossein Azizi; Javad Mirnajafi-Zadeh; Mohammad Javan; Saeed Semnanian
Volume 25, Issue 1 , May and June 2018, , Pages 13-20
Abstract
Background: The locus coeruleus (LC) contains large clusters of noradrenergic neurons which project widely throughout the central nervous system including hypothalamus. The LC is involved in cognitive processes, including attention, learning, memory and drug addiction. Orexin neuropeptides excite the ...
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Background: The locus coeruleus (LC) contains large clusters of noradrenergic neurons which project widely throughout the central nervous system including hypothalamus. The LC is involved in cognitive processes, including attention, learning, memory and drug addiction. Orexin neuropeptides excite the noradrenergic LC neurons; however, its effects on inhibitory synaptic transmission to the LC neurons are unknown. Materials and Methods: Here, we investigated the effect of orexin-A (100 nM) on sIPSCs in LC neurons. We used whole-cell patch clamp recording in rat horizontal slices containing the LC nucleus. Results: Our electrophysiological data indicate that orexin-A application only decreased sIPSCs frequency of LC neurons that was blocked by SB-334867, selective orexin type-1 receptors. Conclusion: In this study, our findings suggest that orexin-A depresses sIPSCs frequency through orexin type-1 receptors. It can be deduced that these changes in inhibitory synaptic transmission may be elicited by prestsynaptic mechanism. These results provide in vitro evidence for a critical role of orexin signaling in LC neurons.