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A role for lateral hypothalamic orexin neurons in reward seeking
Glenda C Harris1, Mathieu Wimmer, Gary Aston-Jones
1Laboratory of Neuromodulation and Behavior, Department of Psychiatry, University of Pennsylvania, 705 Stellar Chance/6100 422 Curie Blvd, Philadelphia, Pennsylvania 19104-6100, USA. glenda@dolphin.upenn.edu
Nature
|August 16, 2005
Summary
Lateral hypothalamus orexin neurons are crucial for reward-seeking behaviors and drug relapse. Activating these neurons promotes reward cue preference and reinstates drug-seeking, highlighting their role in addiction.
Area of Science:
- Neuroscience
- Neurobiology
- Addiction Research
Background:
- The lateral hypothalamus is historically linked to reward and motivation.
- Orexins (hypocretins) are neuropeptides found in lateral hypothalamus neurons.
- Previous studies suggest orexin neurons' role in arousal, sleep, feeding, and reward.
Purpose of the Study:
- To investigate the role of lateral hypothalamus orexin neurons in reward-seeking behaviors.
- To determine if orexin neurons are involved in drug and food reward.
- To explore the potential of orexin signaling in drug relapse and addiction.
Main Methods:
- Activation of lateral hypothalamus orexin neurons.
- Behavioral assays measuring preference for drug and food reward cues.
- Chemogenetic activation to reinstate extinguished drug-seeking behavior.
- Administration of orexin A antagonists and direct orexin A peptide into the ventral tegmental area.
Main Results:
- Activation of lateral hypothalamus orexin neurons strongly correlated with preference for drug and food reward cues.
- Chemical activation of these neurons reinstated extinguished drug-seeking behavior.
- Orexin A antagonism blocked the reinstatement of drug-seeking behavior.
- Direct orexin A administration into the ventral tegmental area also reinstated drug-seeking behavior.
Conclusions:
- Lateral hypothalamus orexin neurons play a significant role in reward-seeking behaviors.
- These neurons are implicated in drug relapse and addiction.
- Orexin signaling in the ventral tegmental area is critical for drug-seeking behavior.
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