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: Lisa M Schrott, Mary Irene Baumgart, Xuewei Zhang, Sheldon B Sparber
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 303 Issue 1 Pg. 257-64 (Oct 2002) ISSN: 0022-3565 [Print] United States
• PMID: 12235259 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Narcotics
• Receptors, Serotonin
• Ritanserin
• paracymethadol
• Naloxone
• Methadyl Acetate
• 1-Methyl-3-isobutylxanthine
• Corticosterone

Topics

• 1-Methyl-3-isobutylxanthine (pharmacology)
• Animals
• Chick Embryo
• Corticosterone (blood)
• Disease Models, Animal
• Hypothalamo-Hypophyseal System (drug effects, physiology)
• Methadyl Acetate (analogs & derivatives, toxicity)
• Morphogenesis
• Naloxone (antagonists & inhibitors, toxicity)
• Narcotics (toxicity)
• Pituitary-Adrenal System (drug effects, physiology)
• Receptors, Serotonin (drug effects, physiology)
• Ritanserin (pharmacology)
• Substance Withdrawal Syndrome