In an article in the February 16, 2006, issue of Neuron, Antonello Bonci and colleagues established that a short protein, or peptide, called orexin A acts on a brain region central to the adaptation to addictive drugs. Specifically, they found in their studies with rats that orexin A induces an adaptation that is necessary for the development of behaviors associated with drug-craving in human addicts. The latest findings follow an earlier discovery by the same group that another molecule, corticotropin releasing factor (CRF), acts similarly.
Such adaptations are believed to create a need that is far more compelling than the simple memory of drug-induced pleasure and represent a "rewiring" of the brain into an addictive state.
In a preview article on the paper in the same issue of Neuron, NIH neuroscientist Roy Wise commented that "Inasmuch as arousal or stress can trigger drug-seeking in drug-free animals, the neuroadaptations discovered by the Bonci group are important not only for how rewarding the drug is after an animal starts taking it, but, perhaps more importantly, for how likely the animal is to initiate drug-seeking during periods of abstinence.
"Because it is during periods of abstinence, not periods of intoxication, that addicts seek treatment, the peptide signaling pathways for orexin and CRF may prove to be fruitful targets in the search for addiction medications."
Bonci and his colleagues based their experiments on past studies by other researchers showing that orexins are important regulatory peptides released by a brain center called the lateral hypothalamus. It was also known that orexins tend to activate circuitry in a region called the ventral tegmental area (VT