The discovery by neuroscientists at UCSF's Ernest Gallo Clinic and Research Center is being reported February 16 in the journal Neuron.
The research focused on orexin's role in strengthening communication between neurons that release dopamine, a brain chemical central to learning and memory. The strengthened communication is known to play a key role in the experience of a drug high and subsequent drug craving.
Orexin is produced in the brain's lateral hypothalmus (LH) region. The scientists demonstrated in studies of rats that orexin acutely enhances the ability of receptors at dopamine neuron synapses known as NMDA receptors to promote the release of dopamine.
They showed that orexin creates a long-lasting potential for strengthened transmission between neurons of the LH region and dopamine-releasing neurons in a brain region known as the ventral tegmental area (VTA). This fundamental change in the neurons, called synaptic plasticity, is known to be critical for new learning and memory formation essential to addiction.
The researchers also showed that blocking normal orexin action in the VTA weakened this critical neuron-to-neuron communication and reversed cocaine-craving behavior in rats.
"This is an exciting finding," said Antonello Bonci, MD, senior author of the paper and UCSF associate professor of neurology, Howard J. Weinberger Chair in Addiction Research and principal investigator at the Gallo Center. "Not only can we see that orexin directly enables the neural communication underlying the development of addiction, but the research points to a novel target in the circuitry of addicti
Contact: Wallace Ravven
University of California - San Francisco