Swallowing disorder and inhibition of cough reflex induced by atropine sulfate in conscious dogs.

In this study, the effects of atropine sulfate (atropine) on swallowing and cough reflex were evaluated in the two experimental models in conscious dogs. To evaluate the effects of atropine on swallowing, 1 mL of marker (contrast medium) was injected into the pharynx under X-ray exposure to induce swallowing. Baclofen, used as a positive control, caused marker congestion in the upper esophagus.

QT PRODACT: in vivo QT assay in the conscious dog for assessing the potential for QT interval prolongation by human pharmaceuticals.

The goal of the present study was to examine the utility of the conscious dog model by assessing the QT-interval-prolonging potential of ten positive compounds that have been reported to induce QT interval prolongation in clinical use and seven negative compounds considered not to have such an effect. Three doses of test compounds or vehicle were administered orally to male beagle dogs (n=4), and telemetry signals were recorded for 24 h after administration. All positive compounds (astemizole, bepridil, cisapride, E-4031, haloperidol, MK-499, pimozide, quinidine, terfenadine, and thioridazine) caused a significant increase in the corrected QT (QTc) interval, with a greater than 10% increase achieved at high doses.

Perinatal exposure to PTU delays switching from NR2B to NR2A subunits of the NMDA receptor in the rat cerebellum.

Certain kinds of developmental neurotoxicants are considered to act by affecting the levels of thyroid hormones, which are essential for the brain development of both humans and experimental animals. Hypothyroidism experimentally induced in rats with propylthiouracil (PTU) offers a useful animal model for developmental neurotoxicity. The purpose of the present study was to clarify developmental alterations in gene expression caused by PTU in this model, with the focus on eight genes implicated in neural network formation or synaptic functions, such as the brain-derived neurotrophic factor (BDNF) and NMDA receptors 2A/2B.

Effects of hypothyroidism induced by perinatal exposure to PTU on rat behavior and synaptic gene expression.

Hypothyroidism in the rat induced by perinatal exposure to propylthiouracil (PTU) is a useful animal model to study molecular changes underlying neurobehavioral defects associated with this condition. Understanding the developmental alterations in gene expression related to the neurobehavioral dysfunction should help to identify molecular markers for developmental neurotoxicity at an early stage of development. In the present study, we evaluate the effects of PTU on the expression of a set of genes implicated in neural network formation or synaptic function at a minimal dose of PTU causing behavioral alteration.