“…Previous evidence also demonstrated the role of orexin-producing neurons projecting to the limbic regions in anxiety and stress responses (Johnson et al 2012). Additionally, it was previously reported that orexin can function in the amygdala to modulate anxiety-related behavior during addiction (Avolio et al 2011). Although orexin A or the orexin receptor antagonist locally microinjected into the hippocampal DG region interfered with morphineinduced CPP in our present study, the possibility that this effect was due to the anxiety associated with increased orexin A levels in the DG cannot be excluded.…”
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.
“…Previous evidence also demonstrated the role of orexin-producing neurons projecting to the limbic regions in anxiety and stress responses (Johnson et al 2012). Additionally, it was previously reported that orexin can function in the amygdala to modulate anxiety-related behavior during addiction (Avolio et al 2011). Although orexin A or the orexin receptor antagonist locally microinjected into the hippocampal DG region interfered with morphineinduced CPP in our present study, the possibility that this effect was due to the anxiety associated with increased orexin A levels in the DG cannot be excluded.…”
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.
“…Intra-CeA Hcrt infusion elevates anxiety levels [34], and Hcrt slice application excites “low-threshold burst” output neurons in the medial division of the CeA [35]. Together with evidence that i.c.v.…”
Section: Hypocretin Modulation In the Bnst And Amygdalamentioning
confidence: 99%
“…Together with evidence that i.c.v. Hcrt activates CeA-CRF neurons [23], these data suggest a mechanism in which Hcrt potentiation of CeA excitability underlies a stress-like state (perhaps by releasing output neurons from inhibitory GABAergic control [34]). Elsewhere in the amygdala, Arendt et al used RNA interference in adult mice to show that BLAHcrtR2 signaling is anxiolytic rather than anxiogenic [36].…”
Section: Hypocretin Modulation In the Bnst And Amygdalamentioning
Hypocretin (also known as orexin) is a peptide neuromodulator that is expressed exclusively in the lateral hypothalamic area and plays a fundamental role in wakefulness and arousal. Chronic stress and compulsive drug-seeking are two examples of dysregulated states of hyperarousal that are influenced by hypocretin transmission throughout hypothalamic, extended amygdala, brainstem, and mesolimbic pathways. Here, we review current advances in the understanding of hypocretin's modulatory actions underlying conditions of negative and positive emotional valence, focusing particularly on mechanisms that facilitate adaptive (and maladaptive) responses to stressful or rewarding environmental stimuli. We conclude by discussing progress toward integrated theories for hypocretin modulation of divergent behavioral domains.
“…Furthermore, endogenous orexins may be involved in producing anxiety in these models, because the OX 2 SORA TCSOX 2 29, but not the partial OX 1 SORA SB-334867, reduced the anxiogenic response in a foot shock-induced anxiety model. The use of elevated plusmaze and light-dark exploration in the Syrian golden hamster showed an anxiogenic response for orexins in the amygdala and an interaction with GABAergic signals (Avolio et al, 2011). In fact, decreased GABA levels have been reported in those suffering from panic disorder (Goddard et al, 2001).…”
Section: A Central Modulation Of Behavior and Physiology By Orexin Smentioning
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