On the selection of mice for haloperidol response and non-response

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Abstract
Mice have been selected over eight generations for response and non-response to haloperidol-induced catalepsy. The selection has been asymmetric, with significantly faster divergence for the haloperidol nonresponder (HNR) line as compared to the haloperidol responder (HR) line. After six generations of selection, the ED50 in the HNR line was 4.3 mg/kg and 0.4 mg/kg in the HR line. Spiroperidol, fluphenazine and trifluoperazine showed a 10-fold or greater discrimination between lines. Raclopride, a specific dopamine D2 antagonist, showed a 7-fold discrimination between lines. Chlorpromazine, thiothixene, (+) butaclamol and cisflupenthixol showed a 3–4-fold discrimination between lines. The specific D1 antagonist, SCH 23390, was the most potent cataleptogenic agent tested (ED50 = 0.1 mg/kg) and did not discriminate between the lines. The HR and HNR lines did not differ in post-synaptic D2 receptor affinity or density as assessed by quantitative receptor autoradiography and membrane binding assays. However, A-9 somatodendritic receptor density was 80% higher in the HNR line as compared to the HR line.