This protocol focuses one component of the endogenous opioid system (EOS), the endogenous dynorphin opioids and the kappa receptors to which they predominantly bind. the alterations in the functional connections between the dynorphin/kappa system and the hypothalamic-pituitayr-adrenal (HPA) axis, modulated by different addictions, are assessed by measuring ACTH and cortisol release after the administration of dynorphin peptides in normal volunteers and in patients in different stages of well-characterized addictions. Similar alterations in the connections between the nynorphin/kappa system and the central dopaminergic system are assessed by measuring prolactin release. Psychological assessments are also made during dynorphin administration in an attempt to quantify any subjective effects. Dynorphin is administered in different doses to the different well-characterized subject groups to elucidate dose response relationships. In addition, dynorphin is administered after pretreatment with different opioid antagonists, in order to elucidate the site of action. the use of antagonists however is not possible in all patient groups, specifically in methadone maintained patients, as severe (but not dangerous) symptoms of opiate withdrawal would be precipitated.
Showing the most recent 10 out of 461 publications