The problem of antipsychotic treatment for functional imaging in Huntington's disease: receptor binding, gene expression and locomotor activity after sub-chronic administration and wash-out of haloperidol in the rat

It has been demonstrated that withdrawal from chronic treatment with haloperidol is associated with a long-lasting increase in the number of striatal dopamine D-2, receptors and variable changes in D-1, receptors. We have investigated the effect of withdrawal from sub-chronic administration of haloperidol on the density of dopamine receptors, dopamine receptor gene expression, and spontaneous locomotor activity. Following a 3-week treatment period with haloperidol (1.5 mg/kg, i.p.), spontaneous locomotor activity measurements, autoradiography of D-1, and D-2, receptors and in situ hybridisation histochemistry of D-1, and D-2, mRNA were performed, Using [H-3]raclopride as the ligand, sub-chronic haloperidol administration produced a robust upregulation in D-2 binding in the striatum of rats which correlated with parallel increases in spontaneous locomotor activity from 24 h to 4 weeks. Using, [H-3]SCH23390 as the Ligand, D1 binding was largely unaffected by the drug treatment. Non-significant changes were measured in the striatal expression of D-1, receptor mRNA or the nigral or striatal expression of D-2, receptor mRNA, Our findings have implications for the use of dopaminergic ligands in positron emission tomography (PET) imaging of patients under regimens of chronic neuroleptics in particular in the context of forthcoming trials of neural grafts in Huntington's disease (HD) striatum. (C) 2000 Elsevier Science B.V. All rights reserved.