Effects of repeated treatment with methcathinone, mephedrone, and fenfluramine on intracranial self-stimulation in rats.

RATIONALE: Synthetic cathinones constitute a class of abused drugs that can act at dopamine, norepinephrine, and serotonin transporters (DAT, NET, and SERT, respectively). Intracranial self-stimulation (ICSS) is a preclinical procedure that can be used to evaluate abuse potential of drugs, and prior studies have indicated that abuse-related ICSS effects of monoamine-transporter substrates, including some synthetic cathinones, are positively correlated with drug selectivity for DAT vs. SERT. Abuse potential of drugs can also be influenced by regimens of repeated drug exposure, but the role of repeated exposure on abuse-related ICSS effects of synthetic cathinones has not been examined. OBJECTIVES: This study used ICSS to evaluate effects of repeated treatment with the DAT>SERT substrate methcathinone, the DAT

Sex differences in abuse-related neurochemical and behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA) in rats.

3,4-Methylenedioxymethamphetamine (MDMA) is a substrate for dopamine (DA), norepinephrine and serotonin (5HT) transporters that produces greater pharmacological effects on certain endpoints in females than males in both clinical and rodent preclinical studies. To evaluate potential for sex differences in abuse-related MDMA effects, the present study compared MDMA effects on intracranial self-stimulation (ICSS) and on in vivo microdialysis measurements of DA or 5HT in the nucleus accumbens (NAc) in female and male Sprague-Dawley rats. For ICSS studies, electrodes were implanted in the medial forebrain bundle and rats trained to press for electrical stimulation over a range of frequencies (56-158Hz, 0.05 log increments) under a fixed-ratio 1 schedule, and the potency (0.32-3.2mg/kg, 10min pretreatment) and time course (3.2. mg/kg, 10-180min pretreatment) of MDMA effects were determined. For in vivo microdialysis, rats were implanted with bilateral guide cannulae targeting the NAc, and the time course of MDMA effects (1.0-3.2mg/kg, 0-180min) on DA and 5HT was determined. MDMA produced qualitatively similar effects in both sexes on ICSS (both increases in low ICSS rates maintained by low brain-stimulation frequencies and decreases in high ICSS rates maintained by high brain-stimulation frequencies) and microdialysis (increases in both DA and 5HT). The duration and peak levels of both abuse-related ICSS facilitation and increases in NAc DA were longer in females. MDMA was also more potent to increase 5HT in females. These results provide evidence for heightened sensitivity of females to abuse-related behavioral and neurochemical effects of MDMA in rats.

Fitness characteristics of a suburban special weapons and tactics team.

Special Weapons and Tactics (SWAT) operators are specialized law enforcement officers who traditionally perform their duties with higher anticipated workloads because of additional body armor, weapons, and equipment used for enhanced operations and protection. This elevated workload increases the need for SWAT operators to improve or maintain their physical fitness to consistently perform routine operations. Typical tasks require trunk rotation, overhead upper extremity use, upper and lower body strength use, and long waiting periods followed by explosive movements while wearing additional equipment. Eleven male SWAT operators from 1 SWAT team performed flexibility, strength, power, and aerobic capacity tests and a variety of job-related tasks. Data were compared with age- and gender-based normative data. Fitness testing revealed that officers ranked high on tests of muscular strength (leg strength, 90th percentile; bench press, 85th percentile); however, body composition (55th percentile), core body strength, and flexibility ranked lower. Furthermore, aerobic capacity and muscular power had a wide range of scores and were also not ideal to support maximal performance during routine operations. These data can assist exercise specialists choose fitness programs specifically for job-related tasks of SWAT operators when creating fitness programs. Fitness programming for law enforcement should focus on improving aerobic fitness, flexibility, core strength, and muscular power while maintaining muscular strength to meet the needs of these specialized officers.

The Radiation Injury Severity Classification system: an early injury assessment tool for the frontline health-care provider.

Our goal was to adapt current diagnostic methods for radiation overexposure patients into a practical system that can be implemented rapidly and reliably by responders unfamiliar with the effects of radiation. Our Radiation Injury Severity Classification (RISC) system uses clinical and haematological parameters from the prodromal phase of the acute radiation syndrome (ARS) to classify acute radiation injury for purposes of managing treatment disposition. Data from well-documented ARS cases were used to test the RISC system. Three-day summaries were generated for each case. These were individually reviewed by the three physicians most involved with the development of the system to establish both a consensus case score (CCS) and disposition category ranges. 30 volunteer raters from varying health disciplines using the RISC system then each independently rated a random selection of 12 cases for injury severity in a self-trained field-simulation exercise. The CCS identified discrete cut-off ranges for the three disposition categories in both manageable and mass casualty events. The group of raters, after a modest period of self-training, achieved overall levels of pairwise agreement with the CCS category of 0.944 for manageable events and 0.947 for mass casualty situations. In conclusion, an early assessment of the severity of the ARS injury is required for an appropriate disposition determination. The RISC system should produce reasonably accurate and reliable assessments of radiation injury severity within 6-12 hours post exposure despite the probable absence of physical dosimetric data.