Effect of typical and atypical neuroleptic treatment on protachykinin mRNA levels in the striatum of the rat.

A significant population of striatal neurons synthesize the tachykinin peptides substance P and neurokinin A. The synthesis of these neuropeptides is under tonic stimulation by dopaminergic neurotransmission. Since typical and atypical neuroleptic drugs display differential effects on the activity of dopaminergic neurons, we evaluated the effect of typical (haloperidol and prolixin) and atypical (molindone, thioridazine and chlozapine) chronic neuroleptic treatment on protachykinin mRNA levels in the medial aspect of the caudate-putamen by in situ hybridization histochemistry. Both typical and atypical neuroleptics decreased protachykinin mRNA levels by 22-40% relative to saline-injected controls. Clozapine failed to affect protachykinin mRNA levels. The data suggest the hypothesis that decreased striatal protachykinin mRNA levels may not be directly linked to development of extrapyramidal side effects.