Organophosphate Agent Induces ADHD-Like Behaviors via Inhibition of Brain Endocannabinoid-Hydrolyzing Enzyme(s) in Adolescent Male Rats.

Anticholinergic organophosphate (OP) agents act on the diverse serine hydrolases, thereby revealing unexpected biological effects. Epidemiological studies indicate a relationship between the OP exposure and development of attention-deficit/hyperactivity disorder (ADHD)-like symptoms, whereas no plausible mechanism for the OP-induced ADHD has been established. The present investigation employs ethyl octylphosphonofluoridate (EOPF) as an OP-probe, which is an extremely potent inhibitor of endocannabinoid (EC, anandamide and 2-arachidonoylglycerol)-hydrolyzing enzymes: that is, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). An ex vivo experiment shows that EOPF treatment decreases FAAH and MAGL activities and conversely increases EC levels in the rat brain. Subsequently, EOPF (treated intraperitoneally once at 0, 1, 2, or 3 mg/kg) clearly induces ADHD-like behaviors (in elevated plus-maze test) in both Wistar and spontaneously hypertensive rats. The EOPF-induced behaviors are reduced by a concomitant administration of cannabinoid receptor inverse agonist SLV-319. Accordingly, the EC system is a feasible target for OP-caused ADHD-like behaviors in adolescent rats.

Determination of overall perturbation factors for plane-parallel ionization chambers in electron beams.

Most dosimetry protocols recommend the use of plane-parallel chambers for dose determination in electron beams with energies below 10 MeV. The new IAEA TRS 381 (1997) protocol includes the overall perturbation factor p(Q) that consists of the in-scattering correction factor p(cav) (or P(repl)) and the wall correction factor p(wall) (or P(wall)). In this work, p(Q) for the commonly applied NACP, PTW/Roos and PTW/Markus plane-parallel chambers was determined experimentally. For the NACP plane-parallel chamber, p(Q) was obtained by comparison with a cylindrical Farmer chamber, while for the PTW/Roos and PTW/Markus chambers it was obtained by comparison with the NACP chamber. The values of p(Q) for these plane-parallel chambers were measured as a function of mean electron energies E(z) from 1.7 MeV to 11.5 MeV. It was found that for the NACP and PTW/Roos chambers, p(Q) is independent of energy down to E(z) =1.7 MeV, while for the PTW/Markus chamber it shows a systematic and exponential drop of about 2% with decreasing energy down to E(z) = 2.7 MeV. However, the decrease of p(Q) for E(z) =1.7 MeV was not exponential.