| OCR Text |
Show COLLEGE OF SCIENCE A NOVEL APPROACH TO ASSESSING THE SAFETY OF PAROXETINE Kirstie Kandaris (Wayne Potts) Department of Biology University of Utah The processes currently in place for testing new drugs for FDA approval are expensive, lengthy and inadequate. The first phase in testing a n e w drug is preclinical trials. This phase of testing is typically conducted on animals in individual cages with few environmental stressors. Consequently, these types of tests do not evaluate performance under stress and tend to neglect the importance of synergy among physiological systems. This current lack of sensitivity is responsible in part for why many drugs either fail during clinical trials or are recalled after public release due to unforeseen adverse health consequences. The Potts lab has developed an alternative, more sensitive method for detecting mammalian health consequences, known as the Organismal Performance Assay (OPA). OPAs use genetically diverse wild mice within semi-natural enclosures that must compete against each other for resources such as food, water, territories, and mates. This assay is broad, functional and sensitive because it demands high performance from most physiological systems in order for an individual to be successful. Paroxetine (Paxil) is an anti-depressant currently on the market, but it has been suspected of causing developmental effects in utero and the manufacturer warns against use by pregnant women. W e assessed performance of Paroxetine (Paxil)-exposed mice when competing directly against control individuals in OPAs. Performance of individuals was measured by survivorship, territoriality, and reproductive success. W e hypothesized that Paroxetine-exposed individuals would suffer significant declines in performance compared with the control individuals. W e found that Paroxetine-exposed breeding pairs took significantly longer to produce their first litter (p=0.05) and that these litters were significantly biased towards female offspring (p=0.0021). Offspring that had been exposed to Paroxetine also weighed significantly less at weaning age than the offspring of the controls (p<0.0001). OPA results revealed that Paroxetine-exposed individuals suffered slightly higher mortality (p=0.4438). Paroxetine-exposed males were significantly less dominant (p=0.0112) and had significantly fewer offspring than control males (p=0.0112). Paroxetine-exposed females also had fewer offspring than controls (p=0.1014).These health declines were missed by all previous animal testing methods, thus indicating that OPAs provide superior sensitivity in comparison to traditional testing methods. 80-, 5 60 2<M 0 Male reproductive success -•- Paroxetine -•>- Control p=0.0122 13 18 23 28 Week 33 The proving grounds for Organismal Performance Assays (OPAs) Male reproductive success as a cumulative average number of sons per population Wayne Potts 65 |
