Apomorphine-induced stereotypic cage climbing in mice as a model for studying changes in dopamine receptor...

We have previously confirmed in mice that apomorphine (APO) induces dopamine specific stereotypic cage climbing. Apparent changes in dopamine receptor sensitivity induced by chronic drug administration appear to be measurable by this technique. In the present experiments, murine stereotypic cage climbing was evauated as a model system for assessing the dopamine receptor supersensitivity induced by chronic administration of the potent butyrophenone neuroleptic spiroperidol. Spiroperidol induced a significantly enhanced response induced by APO (about a 7-fold increase) manifest by 48 hr (but not 24 hr) following cessation of the last chronic injection. Time-response analyses demonstrated that the action of test doses of APO (1.0 or 4.5 mg/kg, IP) was significantly prolonged in the chronic-spiroperidol animals relative to controls. The supersensitivity in the spiroperidol-treated animals lasted more than three weeks for each dose of the neuroleptic and the APO dose-response curve was shifted to the left in spiroperidol-treated animals. Results are discussed in terms of the utility of the model for establishing dose-response, time-course, and duration of effect data within the same group of animals.