Special issue on neuropeptides in stress and addiction: Overview.

Stress and addiction are strongly related conditions that feedback onto each other at several levels. For example, exposure to stressors can cause relapse to abuse of diverse substances with addictive properties. Conversely, withdrawal from drugs of abuse, or even the state of craving in the absence of overt withdrawal, can serve as stressors that produce many of the same physiological effects as observed in the acute stress response. Moreover, stresses associated with drug withdrawal act as negative reinforcers that maintain or even augment addictive behaviors. Just as stress contributes to addiction, substance abuse can alter the neurobiological substrates that underlie the stress response, affecting stress sensitivity or ability to cope with stressors. Finally, the high co-morbidity of substance abuse and stressrelated psychiatric disorders, such as post-traumatic stress disorder and depression, underscore the close relationship between stress and addiction and the likelihood of shared mechanisms. Elucidating circuits, neurotransmitters, intracellular signaling molecules, and genes that underlie the complex relationship between stress and addiction is invaluable for guiding treatments for both drug addiction and stress-related psychiatric disorders. Initial research into this area focused on the biogenic amines dopamine, norepinephrine and serotonin, as interfaces between stress and addiction. However, the discovery that peptides coexist with and/or modulate the activity of biogenic amine and amino acid neurotransmitters expanded the horizon and offered novel potential mechanisms through which stress and addiction may be linked. Our goal was to assemble, in a single special issue, the most contemporary research on the role of brain neuropeptides involved in stress and addiction. Notably, certain neuropeptides have received more attention in this issue than others. Contributions from Shalev et al., Wise and Morales, Valentino et al., and Koob focus on corticotropin-releasing factor (CRF), a molecule that orchestrates the stress response and that has been particularly implicated in stress-induced relapse and the negative reinforcing effects of withdrawal that contribute to drug-seeking behavior. Endogenous opioids are obvious candidates that link stress and addiction. Within this peptide family, recent attention has turned toward the dynorphin-