Format

Send to

Choose Destination
J Neurosci. 2009 Sep 9;29(36):11215-25. doi: 10.1523/JNEUROSCI.6096-08.2009.

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

Author information

1
Ernest Gallo Clinic and Research Center, Department of Neurology, , University of California, San Francisco, San Francisco, California 94110, USA. Borgland@interchange.ubc.ca

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.

PMID:
19741128
PMCID:
PMC2771749
DOI:
10.1523/JNEUROSCI.6096-08.2009
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center