title: Prenatal opiate withdrawal activates the chick embryo hypothalamic pituitary-adrenal axis and dilates vitelline blood vessels via serotonin(2) receptors.
abstract: Opiate withdrawal during pregnancy may occur because of voluntary or forced detoxification, or from rapid cycling associated with exposure to short-acting "street" opiates. Thus, animal modeling of prenatal withdrawal and development of potential therapeutic interventions is important. Direct developmental effects of opiates and/or withdrawal can be studied using a chick model. In ovo administration of the long-acting opiate N-desmethyl-l-alpha-noracetylmethadol (NLAAM) induces opiate dependence in the chick embryo. We examined activation of the hypothalamic-pituitary-adrenal (HPA) axis (assessed via serum corticosterone) and hemodynamic changes (assessed as changes in apparent diameter of vitelline (extraembryonic) blood vessels) after chronic NLAAM exposure and naloxone (Nx)-precipitated withdrawal during late stages of embryogenesis. Nx-precipitated withdrawal increased corticosterone 2- to 4.5-fold and diameters of vitelline blood vessels by 15 to 45%. NLAAM exposure itself did not effect these measures. In a second set of experiments, isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor, was injected into eggs with embryos. IBMX similarly increased corticosterone and vitelline vessel diameter, with a similar time course and response magnitude. Previous studies found that serotonin(2) (5-HT(2)) receptors were involved in other withdrawal manifestations, so we determined whether they were likewise involved. Pretreatment with the 5-HT(2) antagonist ritanserin completely blocked HPA axis activation and vasodilation associated with both Nx-precipitated withdrawal and IBMX administration. This indicates that 5-HT(2) receptors, directly or indirectly, mediate these withdrawal manifestations in the chick embryo.
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA. schro041@umn.edu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Schrott
authors.forename: Mary Irene
authors.initials: MI
authors.lastname: Baumgart
authors.forename: Xuewei
authors.initials: X
authors.lastname: Zhang
authors.forename: Sheldon B
authors.initials: SB
authors.lastname: Sparber
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002642:Chick Embryo; D003345:Corticosterone / Q000097:blood*; D004195:Disease Models, Animal; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D008692:Methadyl Acetate / Q000031:analogs & derivatives* / Q000633:toxicity; D009024:Morphogenesis; D009270:Naloxone / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009294:Narcotics / Q000633:toxicity*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D016713:Ritanserin / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome
chemical_list: D009294:Narcotics; D011985:Receptors, Serotonin; D016713:Ritanserin; C020783:paracymethadol; D009270:Naloxone; D008692:Methadyl Acetate; D015056:1-Methyl-3-isobutylxanthine; D003345:Corticosterone