TY - JOUR T1 - Suppressed Prolactin Response to Dynorphin A<sub>1–13</sub> in Methadone-Maintained Versus Control Subjects JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 581 LP - 587 DO - 10.1124/jpet.103.050682 VL - 306 IS - 2 AU - Gavin Bart AU - Lisa Borg AU - James H. Schluger AU - Mark Green AU - Ann Ho AU - Mary Jeanne Kreek Y1 - 2003/08/01 UR - http://jpet.aspetjournals.org/content/306/2/581.abstract N2 - Dynorphin A1–13, a shortened sequence of the natural peptide dynorphin A1–17, is a primarily κ-opioid receptor-preferring peptide. Previously, we showed that dynorphin A1–13 administered to normal volunteers causes a prompt dose-dependent elevation in serum prolactin that may reflect a reduction in tuberoinfundibular dopaminergic tone. This study was conducted to determine whether tuberoinfundibular dopaminergic tone is reduced in methadone-maintained patients. Eight former heroin addicts on stable-dose methadone maintenance with no ongoing drug or alcohol abuse or dependence and 15 normal volunteer controls with no history of drug or alcohol dependence received dynorphin A1–13 intravenously at doses of 120 μg/kg and 500 μg/kg. Studies began one hour before methadone dosing to avoid the expected increase in prolactin that coincides with peak plasma levels of methadone. After intravenous dynorphin A1–13, a dose-response increase in serum prolactin, which peaked within 20 min, was observed in both groups. There was no difference in prolactin between the two groups at baseline or following a placebo. The prolactin response to each dose of dynorphin A1–13 was significantly lower in the methadone-maintained volunteers compared with the controls. These results suggest that tuberoinfundibular dopaminergic tone is altered in methadone-maintained subjects. It is unknown whether altered dopaminergic tone existed before opiate addiction, is a result of heroin addiction, or is reflective of methadone maintenance. Whether methadone-maintained subjects also have decreased dopaminergic response to dynorphin and other κ-opioid receptor ligands in mesolimbic-mesocortical and nigrostriatal dopaminergic systems cannot be determined from this study. The American Society for Pharmacology and Experimental Therapeutics ER -