"Hypocretin/Orexin Regulation of Dopamine Signaling Impacts Motivated Behavior"

Tuesday, September 19, 2017
4:30 PM - 6:00 PM (ET)
Event Type
Distinguished Visitors Program

 Distinguished Visitor Rodrigo España, Assistant Professor of Neurobiology & Anatomy, Drexel University

 Amassing evidence suggests that the hypocretin system regulates reinforcement processes via actions on the mesolimbic dopamine system. Using behavioral, neurochemical, and genetic techniques we have embarked on a series of studies to examine hypocretin influence on motivated behavior and dopamine signaling. We have demonstrated that augmenting hypocretin neurotransmission promotes cocaine self-administration and enhances dopamine responses to cocaine, while blockade of hypocretin receptor 1 produces the opposite effects. Consistent with this, mice lacking hypocretin peptides or rats with hypocretin receptor 1 knock down display disrupted behavioral and dopamine responses to cocaine. In recent, unpublished work, we observed a novel feature of hypocretin receptor 1 blockade in which a single treatment with a hypocretin receptor 1 antagonist produces lasting reductions in dopamine transporter sensitivity to cocaine. These effects extend beyond the on-board, pharmacological effects of the antagonist indicating that hypocretin receptor 1 blockade elicits lasting dopamine terminal alterations that may influence future cocaine-associated behavior. Together, these observations demonstrate that the hypocretin system influences motivated behavior via alterations in dopamine signaling and suggests this system as a potential pharmacotherapeutic target for the treatment of cocaine addiction.


Sponsored by the Department of Psychology and the Neuroscience Program in conjunction with the Distinguished Visitors Program 

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