Cutaneous Radiation Injuries: Models, Assessment and Treatments.

Many cases of human exposures to high-dose radiation have been documented, including individuals exposed during the detonation of atomic bombs in Hiroshima and Nagasaki, nuclear power plant disasters (e.g., Chernobyl), as well as industrial and medical accidents.

Basal ganglia dopamine loss due to defect in purine recycling.

Several rare inherited disorders have provided valuable experiments of nature highlighting specific biological processes of particular importance to the survival or function of midbrain dopamine neurons. In both humans and mice, deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) is associated with profound loss of striatal dopamine, with relative preservation of other neurotransmitters. In the current studies of knockout mice, no morphological signs of abnormal development or degeneration were found in an exhaustive battery that included stereological and morphometric measures of midbrain dopamine neurons, electron microscopic studies of striatal axons and terminals, and stains for degeneration or gliosis.

Expression of c-FOS in the brain after activation of L-type calcium channels.

In rodents, administration of the L-type calcium channel activators, +/-Bay K 8644 and FPL 64176, causes an unusual neurobehavioral syndrome that includes dystonia and self-injurious biting. To determine the regional influence of these drugs in the brain, the induction of c-FOS was mapped after administration of these drugs to mice. In situ hybridization with an antisense riboprobe directed to c-FOS mRNA revealed widespread induction, with the highest levels in the striatum, cortex, hippocampus, locus coeruleus, and cerebellum.

Self-biting induced by activation of L-type calcium channels in mice: dopaminergic influences.

The L-type calcium channel activator +/-Bay K 8644 induces repetitive self-biting and self-injurious behavior in young mice. Since dopaminergic systems have been implicated in prior studies of these behaviors in both humans and animals, the present experiments were designed to test whether drugs influencing the dopaminergic systems could modify the behavioral responses to +/-Bay K 8644. The ability of +/-Bay K 8644 to provoke self-biting and self-injurious behavior was increased by amphetamine and GBR 12909, drugs that augment synaptic dopaminergic concentrations by blocking the reuptake and/or stimulating the release of dopamine.

Self-biting induced by activation of L-type calcium channels in mice: serotonergic influences.

The L-type calcium channel activator +/-Bay K 8644 has recently been shown to provoke self-injurious biting in young mice. Since the serotonergic systems have been implicated in the expression of self-injurious behavior in both humans and animals, the present studies tested whether drugs influencing serotonin systems could modify the ability of +/-Bay K 8644 to cause this behavior. The ability of +/-Bay K 8644 to provoke self-biting behavior was increased by the serotonin uptake inhibitor fluoxetine or the monoamine oxidase inhibitor clorgyline.

Pharmacologic thresholds for self-injurious behavior in a genetic mouse model of Lesch-Nyhan disease.

Congenital deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) causes Lesch-Nyhan disease in humans, which is associated with severe and recurrent self-injurious behavior (SIB). The HPRT-deficient knockout mouse model, however, does not display this unusual behavior. The present studies tested whether these mice might be more vulnerable to pharmacologic agents known to cause SIB in normal rodents, including clonidine, Bay K 8644, GBR 12909, methamphetamine, pemoline and caffeine.