Effect of Prolonged Treatment with Neuroleptics on Dopamine D‐1 and D‐2 Receptor Density in Corpus Striatum of Mice

Abstract

The effects of long-term treatment with neuroleptics on D-1 and D-2 receptor parameters in corpus striatum were studied in mice. Mice were treated daily for 12 days with the selective D-1 antagonist, the benzazepine SCH 23390, the mixed D-1/D-2 antagonist zuclopenthixol or the selective D-2 antagonist haloperidol. Three days after withdrawal B_max and K_D for ³H-SCH 23390 binding to D-1 receptors and ³H-spiperone binding to D-2 receptors were determined. The study showed that the density of D-2 receptors increased after haloperidol whereas no changes were seen after SCH 23390 or zuclopenthixol. No changes in D-1-receptor density were seen after either treatment. The results are in full agreement with published behavioural results where haloperidol induces tolerance whereas SCH 23390 or zuclopenthixol do not. Some changes in K_D values were seen. The cause and meaning of these changes await further investigation.