Clozapine pre-treatment enhances raclopride catalepsy

The clinical replacement of clozapine by another antipsychotic sometimes ca uses extrapyramidal signs, including dystonia, to appear suddenly. The pres ent study was done, therefore, to test whether clozapine pre-treatment of r ats could affect raclopride-induced catalepsy. Clozapine, at 5 mg/kg, given 2 h before a catalepsy-threshold dose of 0.1 mg/kg raclopride, markedly en hanced raclopride-induced catalepsy in the rats. The results are compatible with earlier in vitro data where pre-exposure of human cloned dopamine D-2 receptors to clozapine resulted in an increased potency of raclopride in i nhibiting the binding of [H-3]clozapine to the receptors. The mechanism of clozapine potentiation of raclopride action may contribute to the clinicall y observed post-clozapine dystonia. (C) 1999 Elsevier Science B.V. All righ ts reserved.