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Effect of Quinine on Autoreceptor‐Regulated Dopamine Release in the Rat Striatum
Author(s) -
Tanaka Takahiko,
Vincent Steven R.,
Nomikos George G.,
Fibiger Hans C.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb10993.x
Subject(s) - autoreceptor , quinpirole , sulpiride , chemistry , microdialysis , agonist , dopamine , striatum , endocrinology , medicine , pharmacology , dopamine receptor , receptor , biology , dopaminergic , biochemistry
In vivo brain microdialysis was used to examine the role of potassium channel activation in dopamine (DA) autoreceptor function in the striatum of freely moving rats. Local application of the D 2 receptor agonists quinpirole or N‐0437 through the dialysis probe significantly reduced extracellular concentrations of DA. Local application of the D 2 antagonist (—)‐sulpiride produced significant increases in DA. Local perfusion with quinine, a K + channel blocker, completely blocked the (—)‐sulpiride‐induced increases in DA but did not affect the DA agonist‐induced decreases. (—)‐Sulpiride completely blocked the effect of quinpirole on DA both in control and in quinine‐treated animals. At the highest dose used, quinine caused a large transient increase in extracellular DA. Local application of tetrodotoxin or infusion of Mg 2+ in the absence of Ca 2+ did not prevent this quinine‐induced transient increase in extracellular DA. These results demonstrate that DA autoreceptors in the striatum regulate DA release in awake, behaving animals. Local application of (—)‐sulpiride increases DA levels by blocking the tonic activation of autoreceptors by endogenous DA. Quinine blocks the neuroleptic‐induced increase in DA, perhaps by preventing the K + channel opening that would normally accompany endogenous autoreceptor activation. The fact that exogenously applied DA receptor agonists can decrease extracellular DA levels in the presence of quinine suggests that they may be acting at extrasynaptic autoreceptors that are not tonically active in vivo. The effect of DA agonists on this site is via a DA receptor because it is blocked by (—)‐sulpiride. However, this receptor does not appear to be coupled to a quinine‐sensitive potassium channel.