Orexin-A-induced ERK1/2 activation reverses impaired spatial learning and memory in pentylenetetrazol-kindled rats via OX1R-mediated hippocampal neurogenesis

Zhao, Xuan; Zhang, Rui xue; Tang, Shi; Ren, Yan; Wu, Yang; Liu, Xiao Min; Ji, Tang

doi:10.1016/j.peptides.2013.11.019

Cited by 60 publications

(44 citation statements)

References 42 publications

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“…Our ELISA results also showed an upregulated level of orexin A in the DG after morphine withdrawal (on day 6). Furthermore, a recent study showed that intra-DG injection of orexin A improved the ability of learning and memory in the epilepsy model induced by pentylenetetrazol (Zhao et al 2013). Hence, it was postulated that withdrawal from morphine induced the release of orexin A and activated the AKT signaling in the DG and that pre-treatment with SB334867 on day 6 only transiently attenuated the effect of orexin A and then partially inhibited morphine-induced CPP.…”

Section: Discussionmentioning

confidence: 99%

“…For example, orexin A induced hippocampal long-term plasticity through the co-activation of multiple kinases, such as protein kinase C, protein kinase A and CaMKII (Selbach et al 2010), and the activation of ERK1/2 in the hippocampus induced by orexin A reverses impaired spatial learning and memory in pentylenetetrazol-kindled rats (Zhao et al 2013). It was recently discovered that the inhibition of OXR1 disrupted the activation of CREB in the dorsal hippocampus and suppressed the rewarding behavior induced by morphine (Riahi, Khodagholi & Haghparast 2013).…”

Section: Discussionmentioning

confidence: 99%

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Orexin A-mediated AKT signaling in the dentate gyrus contributes to the acquisition, expression and reinstatement of morphine-induced conditioned place preference

et al. 2015

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Accumulating evidence indicates that the hippocampal dentate gyrus (DG), a critical brain region contributing to learning and memory, is involved in the addiction and relapse to abused drugs. Emerging studies also suggest the role of orexin signaling in the rewarding behavior induced by repeated exposure to opiates. In the present study, we investigated the dynamic adaptation of orexin signaling in the DG and its functional significance in the acquisition, expression, maintenance of and relapse to rewarding behavior induced by morphine. Repeated place conditioning with morphine significantly increased the orexin A content released from the lateral hypothalamic area projecting neurons into the DG. Local infusions of orexin A into the DG sensitized the acquisition of and relapse to the conditioned place preference induced by morphine. The application of the orexin receptor type 1 (OXR1) antagonist SB334867 significantly abolished the acquisition, expression and maintenance of the conditioned place preference induced by repeated exposure to morphine. Furthermore, the significant increase of the phosphorylation of AKT in the DG was associated with preference for the morphine-paired chamber in rats, which was reversed by the local administration of an OXR1 antagonist. Thus, these findings suggested that the dynamic upregulation of orexin A signaling, via the AKT pathway in the DG, may promote the acquisition and maintenance of opioid-induced craving behaviors and may increase sensitivity to the rewarding effect of subsequent opioids.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Orexin A-mediated AKT signaling in the dentate gyrus contributes to the acquisition, expression and reinstatement of morphine-induced conditioned place preference

et al. 2015

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“…The effects of dentate gyrus-OX1Rs antagonization on LTP occurred also in freely moving rats impairing spatial memory in Morris water maze (Wayner et al, 2004). Some studies examined the effects of the administration of orexin-A in rats treated with Pentylenetetrazol (PTZ) (Zhao et al, 2014). PTZ induces seizures resulting in the hippocampal atrophy, learning and memory deficits and decrease of cerebrospinal fluid-level of orexin-A (Coppola et al, 2010), while the intracerebroventricular injection of orexin-A in PTZ-kindled rats tend to attenuate these impairments, enhancing neurogenesis in the dentate gyrus (Zhao et al, 2014).…”

Section: Links With Brainmentioning

confidence: 99%

Orexin System: The Key for a Healthy Life

et al. 2017

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The orexin-A/hypocretin-1 and orexin-B/hypocretin-2 are neuropeptides synthesized by a cluster of neurons in the lateral hypothalamus and perifornical area. Orexin neurons receive a variety of signals related to environmental, physiological and emotional stimuli, and project broadly to the entire CNS. Orexin neurons are “multi-tasking” neurons regulating a set of vital body functions, including sleep/wake states, feeding behavior, energy homeostasis, reward systems, cognition and mood. Furthermore, a dysfunction of orexinergic system may underlie different pathological conditions. A selective loss orexin neurons was found in narcolepsia, supporting the crucial role of orexins in maintaining wakefulness. In animal models, orexin deficiency lead to obesity even if the consume of calories is lower than wildtype counterpart. Reduced physical activity appears the main cause of weight gain in these models resulting in energy imbalance. Orexin signaling promotes obesity resistance via enhanced spontaneous physical activity and energy expenditure regulation and the deficiency/dysfunction in orexins system lead to obesity in animal models despite of lower calories intake than wildtype associated with reduced physical activity. Interestingly, orexinergic neurons show connections to regions involved in cognition and mood regulation, including hippocampus. Orexins enhance hippocampal neurogenesis and improve spatial learning and memory abilities, and mood. Conversely, orexin deficiency results in learning and memory deficits, and depression.

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“…On the other hand, the electrical activity of hippocampal pyramidal neuron seems to be under direct control of the ORX system (Riahi et al, 2015), pinpointing the crucial role of hippocampal neurogenesis in learning and memory (Deng et al, 2009; Jessberger et al, 2009; Coras et al, 2010). Studies of behavior and hippocampal synaptic plasticity indicate that ERK 1/2 activation enhances the induction of long-term potentiation, which contributes to the formation of memories, moreover the improvement in learning and memory mediated by ORX-A involves OX1R-mediated ERK 1/2 activation and hippocampal neurogenesis (Selcher et al, 2003; Zhao et al, 2014). …”

Section: Orexigenic Systemmentioning

confidence: 99%

Role of the Orexin System on the Hypothalamus-Pituitary-Thyroid Axis

Messina

Fusco

Monda

et al. 2016

Front. Neural Circuits

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Hypocretin/orexin (ORX) are two hypothalamic neuropeptides discovered in 1998. Since their discovery, they have been one of the most studied neuropeptide systems because of their projecting fields innervating various brain areas. The orexinergic system is tied to sleep-wakefulness cycle, and narcolepsy is a consequence of their system hypofunction. Orexinergic system is also involved in many other autonomic functions such as feeding, thermoregulation, cardiovascular and neuroendocrine regulation. The main aim of this mini review article is to investigate the relationship between ORX and thyroid system regulation. Although knowledge about the ORX system is evolving, its putative effects on hypothalamic-pituitary-thyroid (HPT) axis still appear unclear. We analyzed some studies about ORX control of HPT axis to know better the relationship between them. The studies that were analyzed suggest Hypocretin/ORX to modulate the thyroid regulation, but the nature (excitatory or inhibitory) of this possible interaction remains actually unclear and needs to be confirmed.

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Orexin-A-induced ERK1/2 activation reverses impaired spatial learning and memory in pentylenetetrazol-kindled rats via OX1R-mediated hippocampal neurogenesis

Cited by 60 publications

References 42 publications

Orexin A-mediated AKT signaling in the dentate gyrus contributes to the acquisition, expression and reinstatement of morphine-induced conditioned place preference

Orexin A-mediated AKT signaling in the dentate gyrus contributes to the acquisition, expression and reinstatement of morphine-induced conditioned place preference

Orexin System: The Key for a Healthy Life

Role of the Orexin System on the Hypothalamus-Pituitary-Thyroid Axis

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