Evaluating pharmacological models of high and low anxiety in sheep.

New tests of animal affect and welfare require validation in subjects experiencing putatively different states. Pharmacological manipulations of affective state are advantageous because they can be administered in a standardised fashion, and the duration of their action can be established and tailored to suit the length of a particular test. To this end, the current study aimed to evaluate a pharmacological model of high and low anxiety in an important agricultural and laboratory species, the sheep. Thirty-five 8-month-old female sheep received either an intramuscular injection of the putatively anxiogenic drug 1-(m-chlorophenyl)piperazine (mCPP; 1 mg/kg; n = 12), an intravenous injection of the putatively anxiolytic drug diazepam (0.1 mg/kg; n = 12), or acted as a control (saline intramuscular injection n = 11). Thirty minutes after the treatments, sheep were individually exposed to a variety of tests assessing their general movement, performance in a 'runway task' (moving down a raceway for a food reward), response to startle, and behaviour in isolation. A test to assess feeding motivation was performed 2 days later following administration of the drugs to the same animals in the same manner. The mCPP sheep had poorer performance in the two runway tasks (6.8 and 7.7 × slower respectively than control group; p < 0.001), a greater startle response (1.4 vs. 0.6; p = 0.02), a higher level of movement during isolation (9.1 steps vs. 5.4; p < 0.001), and a lower feeding motivation (1.8 × slower; p < 0.001) than the control group, all of which act as indicators of anxiety. These results show that mCPP is an effective pharmacological model of high anxiety in sheep. Comparatively, the sheep treated with diazepam did not display any differences compared to the control sheep. Thus we suggest that mCPP is an effective treatment to validate future tests aimed at assessing anxiety in sheep, and that future studies should include other subtle indicators of positive affective states, as well as dosage studies, so conclusions on the efficacy of diazepam as a model of low anxiety can be drawn.