In experiments with rat brain slices, the researchers demonstrated that orexin A does increase activity of neurons in the VTA associated with such plasticity.
And in experiments with whole animals, the researchers found that orexin A was required for "behavioral sensitization" to cocaine. This sensitization shows itself as a long-lasting increase in activity by the animals when they receive the drug and is an indicator that the animals are experiencing an increased craving for the drug.
Importantly, when the researchers "microinjected" directly into the VTA region of animals a drug that blocks orexin receptors, they found they could block the development of behavioral sensitization.
"The findings presented here establish a potential mechanism for the role of orexin signaling in plasticity related to addiction," concluded the researchers. The researchers wrote that this orexin-induced plasticity in the VTA "is likely an important substrate of behaviors relevant to addiction, as we show that activation of [orexin] receptors in the VTA is necessary for the development of cocaine-mediated behavioral sensitization. Thus, orexin receptors may provide novel pharmacotherapeutic targets for motivational disorders such as addiction.