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Rats received access to either distilled water, sucrose, quinine, hydrochloric acid, saline, or the three flavors of sucrose, quinine, and hydrochloric followed one or 28-days later by testing for neophobia and training and testing for conditioned taste aversion to saline. At the one-day interval, preexposures to saline, hydrochloric, or multiple flavors attenuated neophobia to saline while only preexposures to saline attenuated the conditioned aversion to saline. At the 28-day interval, none of the preexposure conditions attenuated neophobia to saline while preexposures to saline attenuated the conditioned aversion to saline. / M.S.

The purpose of this study was to investigate the effects of cocaine on spatial memory consolidation using the Morris water maze. Specifically, male and female C57BL/6 mice were trained on a spatial water task, and then administered a single posttraining injection of saline or cocaine (1.25, 2.5, 5.0, or 20.0 mg/kg).

Cynomolgus macaques (Macaca fascicularis) are the most commonly used non-human primate for research and testing in Europe. Their principal use is in preclinical safety testing of new pharmaceuticals to assess risk of adverse effects, as indicated by changes in a core battery of physiological measures before human exposure. Regulatory studies are strictly controlled through legislation and codes of practices underpinned by the principles of humane science, the 3Rs; Replacement, Reduction and Refinement. Despite the link between good welfare and good science now universally made in codes of practice, legislation and the literature, there are few studies aimed at systematically examining the link and almost no quantitative data from cynomolgus macaques used for toxicology. The main aim of this thesis was to examine the link between Refinement, animal welfare and scientific output for this important animal model, piggy-backing on regulatory studies conducted by a large contract research organisation. In the laboratory, animal welfare is formally considered in terms of Refinement which has evolved to include both the reduction of negative welfare states and the proactive enhancement of positive welfare over the animal’s lifetime. A multidisciplinary approach to welfare assessment including measures of behaviour, physiology and physical health, and which built upon current unit procedures was undertaken to produce an overall assessment of welfare in cynomolgus macaques. Macaque facial expressions, vocalisations, activity and position in the home cage, body weight change, body condition and alopecia scores were found to be reliable indicators of welfare state and would be most feasible for care staff to monitor. The concept of quality of scientific output was defined in relation to toxicological findings and includes sensitivity, reliability and repeatability of individual measures in the core battery (e.g. heart rate, blood pressure, haematology, clinical chemistry and organ weights). The link between welfare and quality of scientific output was then systematically explored with Refinements to macaque use in regulatory studies. The first, a data mining study, undertaken to quantify the effects on biological data recorded from cynomolgus macaques, used in regulatory studies over an eight-year period as the CASE sponsor transitioned from single to permanent group housing, found the effects to be highly variable on individual parameters in the core battery and in some instances welfare-positive effects of group housing were confounded by concurrent changes in standard operating procedures. A further study of planned Refinements to macaque-care staff interaction through enhanced socialisation was found to help animals cope better with husbandry and scientific procedures and enhance quality of cardiovascular measures recorded at baseline. In light of these findings a number of recommendations are made including a framework of terms useful for measuring quality of scientific output, a welfare assessment framework and Refinements to husbandry and scientific procedures for cynomolgus macaques used in regulatory toxicology. Because of their capacity to suffer it is both ethically and scientifically important that macaque welfare is maximised and their use results in valid and reliable experimental outcomes informing on the safety and efficacy of new pharmaceuticals prior to human exposure.