RT Journal Article
SR Electronic
T1 Orexin A/Hypocretin-1 Selectively Promotes Motivation for Positive Reinforcers
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 11215
OP 11225
DO 10.1523/JNEUROSCI.6096-08.2009
VO 29
IS 36
A1 Stephanie L. Borgland
A1 Shao-Ju Chang
A1 M. Scott Bowers
A1 Jennifer L. Thompson
A1 Nicole Vittoz
A1 Stan B. Floresco
A1 Jonathan Chou
A1 Billy T. Chen
A1 Antonello Bonci
YR 2009
UL http://www.jneurosci.org/content/29/36/11215.abstract
AB 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.