The d-amphetamine-treated Göttingen miniature pig: an animal model for assessing behavioral effects of antipsychotics

RATIONALE: Rodents are usually used to assess the ability of antipsychotic drugs to antagonize hyperlocomotion induced by dopamine agonists, such as the psychostimulant d-amphetamine. However, the substantial differences between rodents and humans may hinder extrapolation of experimental results to humans. For this reason, we speculated that Göttingen miniature pigs, which show strong physiological and genetic homology with humans, might be a better model for investigating the effects of antipsychotics. To investigate this, we determined whether d-amphetamine induced hyperlocomotion in miniature pigs and whether this effect was reversible by antipsychotics. MATERIALS AND METHODS: d-Amphetamine was tested in the dose range of 0.2 to 2.0 mg kg(−1) for its ability to induce hyperactivity in the open field, and the effects of two antipsychotics, haloperidol and risperidone, on amphetamine-induced hyperactivity were examined. RESULTS: d-Amphetamine increased open-field activity at 0.2, 0.4, and 0.7 mg kg(−1) s.c. but not at higher doses. The stimulation of open-field activity induced by 0.4 mg kg(−1) s.c. d-Amphetamine was antagonized by haloperidol and risperidone (0.01 and 0.04 mg kg(−1) s.c.). CONCLUSION: d-Amphetamine-induced hyperlocomotion in miniature pigs may be a useful model for studying the effect of putative antipsychotics.