Involvement of the cholinergic system in haloperidol-induced release of dopamine from slices of striatum in the rat.
The effects of cholinergic and anticholinergic drugs on spontaneous or haloperidol-induced release of dopamine (DA) were studied in vitro. The slices of striatum were placed in a chamber and continuously superfused with Krebs' solution, containing various concentrations of haloperidol, with or without atropine, d-tubocurarine (d-TC), tetrodotoxin (TTX), physostigmine or carbachol. Haloperidol, enhanced the release of endogenous DA from the slices of striatum at an EC50 value of 25.6 microM. The effect of haloperidol was significantly reduced by atropine (2.5 microM), while it was unaffected by d-TC (10 microM) and TTX (1 microM). In contrast, physostigmine (3.7 microM) significantly increased the haloperidol-induced efflux of DA from the slices of striatum. In addition, acetylcholine (ACh), in the presence of physostigmine or carbachol, enhanced the basal efflux of DA at EC50 values of 2.8 microM and 83 microM, respectively. The effect of ACh on the efflux of DA was antagonized by atropine. These data suggest that haloperidol-induced release of DA is, at least partially, mediated by the activation of muscarinic ACh receptors located in the striatum.
Yamada
S
S
Institute of Brain Diseases, Department of Neuropsychiatry, Kurume, Fukuoka, Japan.
Nishi
S
S
Kojima
H
H
Yokoo
H
H
Tsutsumi
T
T
Inanaga
K
K
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010830:Physostigmine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D013779:Tetrodotoxin; D001285:Atropine; D010830:Physostigmine; D006220:Haloperidol; D000109:Acetylcholine; D004298:Dopamine