Hypocretin (orexin) neuromodulation of stress and reward pathways

Giardino, William J.; Lecea, Luı́s de

doi:10.1016/j.conb.2014.07.006

Cited by 85 publications

(56 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this, intracerebroventricular administration of orexin A induces anxiety-like effects in several behavioral models of anxiety [93]. The existence of reciprocal interactions between orexin and CRF neurons [94] suggests that the orexin system is an important component of the pathways contributing to the physiological CRF-mediated behaviors that occur in response to stressful situations [95]. Dysregulation of stress responses could lead to the development of different anxiety disorders, which might be influenced by the activity of the orexin system, as described in the present review.…”

Section: Stressmentioning

confidence: 67%

Orexins and fear: implications for the treatment of anxiety disorders

Flores

Saravia

Maldonado

et al. 2015

Trends in Neurosciences

View full text Add to dashboard Cite

An understanding of the neurobiological mechanisms involved in the regulation of fear is essential for the development of new treatments for anxiety disorders, such as phobias, panic, and post-traumatic stress disorders (PTSD). Orexins, also known as hypocretins, are neuropeptides located exclusively in hypothalamic neurons that have extensive projections throughout the central nervous system. Although this system was initially believed to be primarily involved in the regulation of feeding behavior, recent studies have shown that orexins also modulate neural circuits implicated in the expression and extinction of fear memories. Here, we discuss recent findings involving orexins in anxiety disorders and current clinical trials using orexin ligands that could be applied to identify new therapies for diseases characterized by pathological fear.

show abstract

Section: Stressmentioning

confidence: 67%

Orexins and fear: implications for the treatment of anxiety disorders

Flores

Saravia

Maldonado

et al. 2015

Trends in Neurosciences

View full text Add to dashboard Cite

show abstract

“…As outlined above, orexin neurons signal at a number of target structures to regulate drug seeking, including VTA [20, 30, 71, 102, 103], PVT [128, 131, 132], and other reward and motivation-related targets [12, 186]. Early work revealed that lateral (LH/PFA) orexin neurons preferentially projected to VTA in rats [187], although orexin neuron projections to VTA in mice appear to originate from both medial and lateral subdivisions [188].…”

Section: Functional Heterogeneity Of Orexin Neurons: a Medial/latermentioning

confidence: 99%

A Decade of Orexin/Hypocretin and Addiction: Where Are We Now?

James

Mahler

Moorman

et al. 2016

Current Topics in Behavioral Neurosciences

151

112

View full text Add to dashboard Cite

One decade ago, our laboratory provided the first direct evidence linking orexin/hypocretin signaling with drug seeking by showing that activation of these neurons promotes conditioned morphine-seeking behavior. In the years since, contributions from many investigators have revealed roles for orexins in addiction for all drugs of abuse tested, but only under select circumstances. We recently proposed that orexins play a fundamentally unified role in coordinating “motivational activation” under numerous behavioral conditions, and here we unpack this hypothesis as it applies to drug addiction. We describe evidence collected over the past 10 years that elaborates the role of orexin in drug seeking under circumstances where high levels of effort are required to obtain the drug, or when motivation for drug reward is augmented by the presence of external stimuli like drug-associated cues/contexts or stressors. Evidence from studies using traditional self-administration and reinstatement models, as well as behavioral economic analyses of drug demand elasticity, clearly delineates a role for orexin in modulating motivational, rather than the primary reinforcing aspects of drug reward. We also discuss the anatomical interconnectedness of the orexin system with wider motivation and reward circuits, with a particular focus on how orexin modulates prefrontal and other glutamatergic inputs onto ventral tegmental area dopamine neurons. Last, we look ahead to the next decade of the research in this area, highlighting the recent FDA approval of the dual orexin receptor antagonist suvorexant (Belsomra®) for the treatment of insomnia as a promising sign of the potential clinical utility of orexin-based therapies for the treatment of addiction.

show abstract

“…There are studies suggesting that nesfatin-1 and orexin-A may be related to many disorders in addition to appetite (10,11,16,37). Moreover, orexin-A has pleiotropic effects, including increasing body temperature, heart rate, and blood pressure by stimulating the sympathetic nervous system (9,38).…”

Section: Orexin-a and Nesfatin-1 In Hyperthyroidismmentioning

confidence: 99%

“…It has been suggested that orexin-A increases both food intake and energy expenditure to prevent weight gain (5). Many publications have shown that orexin-A is related to sleep-wakefulness, arousal, energy balance, narcolepsy, glucose metabolism, gastric ulcers, and thermogenesis (4,(6)(7)(8)(9)(10)(11). The results of animal studies that investigated the relationship of orexin-A with the thyroid axis are contradictory (4,12,13).…”

Section: Introductionmentioning

confidence: 99%