Inhibition of nitric oxide synthase enhances cocaine's developmental toxicity: vascular and CNS effects.

Ischemia and/or reperfusion injury from free radicals may cause cocaine's toxicity, including its effect upon neurobehavioral development. We previously used salicylate to measure hydroxyl free radicals in chick embryos exposed to cocaine. The combination was more toxic than cocaine alone.

HPA axis dysregulation following prenatal opiate exposure and postnatal withdrawal.

We examined the effects of prenatal exposure to the long acting opiate l-alpha-acetylmethadol (LAAM) followed by postnatal withdrawal on hypothalamic-pituitary-adrenal (HPA) axis reactivity in neonatal and adult rats and anxiety-like behavior in adult rats. Female rats were treated with LAAM (0, 0.2, or 1.

Suppressed fever and hypersensitivity responses in chicks prenatally exposed to opiates.

We have established procedures to reliably induce opiate dependence in the chick embryo via in ovo injection, early in embryonic development, of the long-acting and potent opiate N-desmethyl-l-alpha-noracetylmethadol (NLAAM). Prior studies found that there is continual exposure to NLAAM throughout embryogenesis and shortly after hatching there are signs of spontaneous withdrawal. In the present study, we used three doses of NLAAM (2.

Vasoconstriction caused by cocaine is enhanced by sodium salicylate: is inducible nitric oxide synthase mRNA related?

We have previously found that sodium salicylate (NaSal), injected into chicken eggs at nontoxic doses used for quantifying hydroxyl free radicals in hearts and brains of embryos, caused or exacerbated hemorrhages and dramatically reduced hatchability when combined with cocaine (Coc). It has also been reported that inducible nitric oxide synthase (iNOS) gene expression is altered in brain in response to vascular damage and inflammation. In this study we measured diameters of membrane-bound blood vessels (BV) before and after pretreatment with saline (NaCl) or NaSal (100 mg/kg egg), followed by infusion of either NaCl or Coc HCl (total of 67.

Prenatal opiate withdrawal activates the chick embryo hypothalamic pituitary-adrenal axis and dilates vitelline blood vessels via serotonin(2) receptors.

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.