Effect of chronic neuroleptic treatment on central and peripheral muscarinic receptors

The regulation of muscarinic acetylcholine receptor (MAChR) subtypes in rat striatum, bladder and heart was examined following a 14-day administration of neuroleptics (clozapine or fluphenazine), anticholinergics (atropine) or a combination of anticholinergics and neuroleptics. Levels of MAChRs were ascertained by the use of immunoprecipitation and radioligand binding. The combined treatment of fluphenazine and atropine produced an increase in all MAChR subtype levels in striatum with m1 receptor levels having the largest increase (270%) from control. A significant increase (105%) was also seen striatal in m2 receptor levels. Residual muscarinic receptor levels, representing the m3 and m4 subtypes, were increased (72%) to a lesser degree above control. Fluphenazine treatment alone increased levels of the m2 MAChR, whereas clozapine administration had no significant effect on levels of any MAChR subtype in this tissue. Administration of the cholinergic antagonist, atropine, showed a significant increase (89%) in the striatal m1 MAChR subtype. Of the MAChRs found in rat bladder and rat heart, the m2 subtype has been shown to be the most abundant. Results from the rat bladders indicated a reduction (50%) in muscarinic antagonist binding that was limited to the fluphenazine treatment group. In heart, atropine treatment alone produce a slight increase (ca. 10%) in receptor binding. No significant effect on muscarinic receptor levels was seen with the other treatment groups. These data demonstrate that there are differences in muscarinic receptor level modulation between central and peripheral tissues.