Effects of haloperidol and clozapine on preprotachykinin-A messenger RNA, tachykinin tissue levels, release and neurokinin-1 receptors in the striato-nigral system.
The effects of haloperidol and clozapine on tachykinin tissue levels, preprotachykinin-A messenger RNA, spontaneous and potassium-evoked tachykinin release, dopamine D2 receptors, and [125I]Bolton-Hunter-substance P binding sites in the striato-nigral system were examined. Chronic administration (10 days) of the dopamine receptor antagonist haloperidol (2 mg/kg i.p.) significantly decreased tissue levels of substance P like-immunoreactivity and neurokinin A like-immunoreactivity in the striatum and the substantia nigra. The corresponding preprotachykinin-A mRNA was decreased in the striatum. Haloperidol did not affect the potassium-evoked tachykinin release in the substantia nigra but significantly increased the spontaneous release. Haloperidol increased the number of D2-receptors but left [125I]Bolton-Hunter-substance P binding sites, representing neurokinin 1 (NK-1) receptors, as determined by competition experiments with selective ligands, unchanged. Clozapine (30 mg/kg, i.m.) did not influence nigral and striatal tachykinin tissue levels, preprotachykinin-A mRNA and potassium-evoked release or spontaneous efflux in the substantia nigra, or D2-receptors and [125I]Bolton-Hunter-substance P binding sites. The present data indicate that neuroleptics influence the striato-nigral tachykinin system in different ways. Tachykinins may, therefore, contribute to the therapeutic and/or untoward effects of certain neuroleptic drugs.
Department of Psychiatry, University Hospital Innsbruck, Austria.
C
C
Humpel
G A
GA
Knaus
B
B
Auer
H G
HG
Knaus
C
C
Haring
E
E
Theodorsson
A
A
Saria
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003984:Dibenzazepines / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D017448:Receptors, Dopamine D2; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013373:Substance P / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism*
D003984:Dibenzazepines; D011498:Protein Precursors; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D003024:Clozapine; D006220:Haloperidol