MICROINJECTION OF SIGMA-LIGANDS INTO CRANIAL NERVE NUCLEI PRODUCES VACUOUS CHEWING IN RATS

Many typical neuroleptics carry a high risk for producing motor side e ffects in humans, and have significant affinities for sigma (sigma) re ceptors. Sigma receptors are densely concentrated in cranial nerve nuc lei that comprise the final common pathways for lingual, facial and ma sticatory movements; thus, they may serve as important substrates for some of the unwanted movements that can accompany neuroleptic treatmen t, Therefore, the purpose of this study was to evaluate whether microi njection of sigma ligands into the facial nucleus or spinal trigeminal nucleus, oralis would cause orofacial dyskinesias, and whether these effects could be attenuated with sigma receptor antagonists. Microinje ction of the high affinity sigma ligands, di-o-tolyl-guanidine or halo peridol (0-10 nmol/0.5 mu l), produced a marked increase in vacuous ch ewing and facial tremors in rats, while coadministration of the functi onal a antagonists, BD1047 or BD1063 (5 nmol), greatly attenuated thes e drug-induced movements. Sulpiride and clozapine (10 nmol/0.5 mu l), sigma inactive/ dopamine active atypical antipsychotic drugs with a mu ch reduced risk for producing motor side effects in humans; were unabl e to elicit orofacial dyskinesias when microinjected into the facial o r spinal trigeminal nucleus, oralis. These studies indicate that sigma receptors may contribute to some f'orms of motor side effects resulti ng from antipsychotic drug treatment.