On the selection of mice for haloperidol response and non-response.
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 non-responder (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 cis-flupenthixol 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.
Hitzemann
R
R
Department of Psychiatry and Behavioral Sciences, SUNY, Stony Brook 11794-8101.
Dains
K
K
Bier-Langing
C M
CM
Zahniser
N R
NR
D000818:Animals; D001345:Autoradiography; D002375:Catalepsy / Q000139:chemically induced*; D006220:Haloperidol / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D017448:Receptors, Dopamine D2
D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D006220:Haloperidol