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      Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers.

      The Journal of neuroscience : the official journal of the Society for Neuroscience

      Animals, Benzoxazoles, pharmacology, Choice Behavior, drug effects, physiology, Cocaine-Related Disorders, prevention & control, Dietary Fats, administration & dosage, antagonists & inhibitors, Intracellular Signaling Peptides and Proteins, Male, Motivation, Neural Pathways, Neuropeptides, Orexin Receptors, Rats, Rats, Sprague-Dawley, Receptors, G-Protein-Coupled, Receptors, Neuropeptide, Reinforcement (Psychology), Urea, analogs & derivatives

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          Abstract

          Orexin A/hypocretin-1 (oxA/hcrt-1) is known to be a modulator of dopamine-dependent neuronal activity and behaviors. However, the role of this system in driving motivated behaviors remains poorly understood. Here, we show that orexin/hypocretin receptor-1 (ox/hcrt-1R) signaling is important for motivation for highly salient, positive reinforcement. Blockade of ox/hcrt-1R selectively reduced work to self-administer cocaine or high fat food pellets. Moreover, oxA/hcrt-1 strengthened presynaptic glutamatergic inputs to the ventral tegmental area (VTA) only in cocaine or high fat self-administering rats. Finally, oxA/hcrt-1-mediated excitatory synaptic transmission onto VTA neurons was not potentiated following an arousing, aversive stimulus, suggesting that oxA/hcrt-1-mediated glutamatergic synaptic transmission was potentiated selectively with highly salient positive reinforcers. These experiments provide evidence for a selective role of oxA/hcrt-1 signaling in motivation for highly salient reinforcers and may represent a unique opportunity to design novel therapies that selectively reduce excessive drive to consume positive reinforcers of high salience.

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          Journal
          19741128
          2771749
          10.1523/JNEUROSCI.6096-08.2009

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