Premium
Effects of haloperidol and clozapine on preprotachykinin‐A messenger RNA, tachykinin tissue levels, release and neurokinin‐1 receptors in the striato‐nigral system
Author(s) -
Christian Humpel,
Andrea Knaus Gabriele,
Bernhard Auer,
HansGunther Knaus,
Christian Haring,
Elvar Theodorsson,
Alois Saria
Publication year - 1990
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890060102
Subject(s) - substance p , substantia nigra , haloperidol , chemistry , endocrinology , tachykinin receptor , medicine , neurokinin a , pharmacology , receptor , dopamine , clozapine , striatum , neuropeptide , biology , biochemistry , dopaminergic , schizophrenia (object oriented programming) , psychiatry
The effects of haloperidol and clozapine on tachykinin tissue lelvels, preprotachykinin‐A messenger RNA, spontaneous and potassium‐evoked tachykinin release, dopamine D 2 receptors, and [ 125 ]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 ub tge struatyun, Haloperidol did not affect the potassium‐evoked tachyikinin release in the substantia nigra but significantly increased the spontaneous release. Haloperidol increased the number of D 2 ‐receptors but left [ 125 ]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 D 2 ‐receptors and [ 125 I]Bolton‐Hunter‐substance P bindin 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.