ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2022
Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Nucleus of the solitary tract regulation of cue-induced appetitive behaviors via midbrain dopamine neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.Brain sciences · 2026Review
- Activation of LH orexin neurons and VTA dopamine neurons is involved in anesthesia/surgery-induced sleep-wake disorders and delirium-like behaviors in mice.Scientific reports · 2026Article
- Lateral hypothalamic orexinergic neurons as central mediators of pain modulation and non-pharmacological analgesia.Frontiers in pharmacology · 2026Review
- Multisystem regulation of reward and addiction: beyond the dopaminergic system.Frontiers in pharmacology · 2026Review
- Modulatory effects of orexin and dynorphin on stress-related alcohol seeking and relapse: pivotal role of the posterior paraventricular nucleus of the thalamus.Frontiers in pharmacology · 2026Review
- From Monoamines to Systems Psychiatry: Rewiring Depression Science and Care (1960s-2025).Biomedicines · 2025Article
- Review
- The Orexin System in Addiction: Neuromodulatory Interactions and Therapeutic Potential.Brain sciences · 2025Review
- Case series of aripiprazole monotherapy in bipolar disorder with delayed sleep-wake phase syndrome.BMC psychiatry · 2025Article
- What's the occasion? Phasic dopamine signaling and interoception.Current opinion in neurobiology · 2025Review
- Dynorphinergic lateral hypothalamus to posterior ventral tegmental area pathway matures after adolescence in male rats.Neuropharmacology · 2025Article
- Tug-of-War: Orexin and Dynorphin Effects on Reward Processing Circuits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The role of dorsal raphe nucleus neuropeptides in reward and aversion.Frontiers in behavioral neuroscience · 2025Review
- The anxiogenic drug yohimbine is a reinforcer in male and female rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Contribution of hypothalamic orexin (hypocretin) circuits to pathologies of motivation.British journal of pharmacology · 2024Review
- Distinct Neuromodulatory Effects of Endogenous Orexin and Dynorphin Corelease on Projection-Defined Ventral Tegmental Dopamine Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Basolateral amygdala parvalbumin interneurons coordinate oscillations to drive reward behaviors.Current biology : CB · 2024Article
- Stimulation of VTA dopamine inputs to LH upregulates orexin neuronal activity in a DRD2-dependent manner.eLife · 2024Article
- The Formation and Function of the VTA Dopamine System.International journal of molecular sciences · 2024Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reward and reinforcement processes are critical for survival and propagation of genes. While numerous brain systems underlie these processes, a cardinal role is ascribed to mesolimbic dopamine. However, ventral tegmental area (VTA) dopamine neurons receive complex innervation and various neuromodulatory factors, including input from lateral hypothalamic (LH) orexin/hypocretin neurons which also express and co-release the neuropeptide, dynorphin. Dynorphin in the VTA induces aversive conditioning through the Kappa opioid receptor (KOR) and decreases dopamine when administered intra-VTA. Exogenous application of orexin or orexin 1 receptor (oxR1) antagonists in the VTA bidirectionally modulates dopamine-driven motivation and reward-seeking behaviours, including the attribution of motivational value to primary rewards and associated conditioned stimuli. However, the effect of endogenous stimulation of LH orexin/dynorphin-containing projections to the VTA and the potential contribution of co-released dynorphin on mesolimbic dopamine and reward related processes remains uncharacterised. We combined optogenetic, electrochemical, and behavioural approaches to examine this. We found that optical stimulation of LH orexin/dynorphin inputs in the VTA potentiates mesolimbic dopamine neurotransmission in the nucleus accumbens (NAc) core, produces real time and conditioned place preference, and increases the food cue-directed orientation in a Pavlovian conditioning procedure. LH orexin/dynorphin potentiation of NAc dopamine release and real time place preference was blocked by an oxR1, but not KOR antagonist. Thus, rewarding effects associated with optical stimulation of LH orexin/dynorphin inputs in the VTA are predominantly driven by orexin rather than dynorphin.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.