Researchers at the University of Pennsylvania School of Medicine have discovered that the recently identified neurotransmitter orexin (also known as hypocretin) influences reward processing by activating neurons in the lateral hypothalamus region of the brain.
By identifying the relationship between orexin neurons and behaviors associated with reward seeking, drug relapse, and addiction, researchers hope to find new treatments for drug addiction.
Previous studies have linked orexin activity to sleep and arousal (wakefulness), as well as feeding and appetite. Anatomical studies have shown that orexin neurons extend into the brain regions associated with reward pathways, including the ventral tagmental area and nucleus accumbens. Communication between the lateral hypothalamus and these brain regions suggests that orexin neurons may have a role in motivation and reward-seeking behavior. In order to examine the relationship between orexin and reward seeking, Glenda Harris, PhD, working with Gary Aston-Jones, PhD, in the Department of Psychiatry at Penn, examined orexin function in rats using a behavioral test aimed at mimicking food- and drug-reward seeking and drug relapse. This research appeared online in Nature on August 14.
"The lateral hypothalamus has been tied to reward and pleasure for decades, but the specific circuits and chemicals involved have been elusive," says Aston-Jones. "This is the first indication that the neuropeptide orexin is a critical element in reward-seeking and drug addiction. These results provide a novel and specific target for developing new approaches to treat addiction, obesity, and other disorders associated with dysfunctional reward processing."
Harris and Aston-Jones found a strong association between the activation of orexin neurons in the lateral hypothalamus and reward seeking of morphine, cocaine, and food. Using Fos, a chemical marker of neuronal stimulation, the researchers found that the highest levels of activity in the orexin neurons appeared in rats demonstrating the greatest level of reward seeking.