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Rate and Duration of Stimulation Determine Presynaptic Effects of Haloperidol on Dopaminergic Neurons
Author(s) -
Hoffmann Irene S.,
Cubeddu Luigi X.
Publication year - 1982
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.1471-4159.1982.tb03987.x
Subject(s) - haloperidol , apomorphine , stimulation , dopaminergic , chemistry , dopamine , facilitation , dopamine receptor , endocrinology , medicine , neuroscience , biology
Superfused rabbit neostriatal slices prelabeled with [ 3 H]dopamine ([ 3 H]DA) were depolarized with electrical pulses (12 V, 1 ms). Although transmitter release showed a proportional increase with a greater number of pulses (30‐360 pulses), flat frequency‐release curves were obtained. Haloperidol (0.03–0.3 μ m ) enhanced 3 H overflow without affecting its metabolism or time course, and antagonized apomorphine‐induced inhibition of transmitter release. Maximal enhancement of release by haloperidol was obtained with 30–60 pulses delivered at a rate of 3 Hz, whereas much less facilitation of release was seen at 0.3 and 1 Hz (30–90 pulses) or with 360 pulses at either of the three frequencies. Therefore, the slope of the frequency‐release curve was markedly increased by haloperidol. These results indicate that activation of presynaptic DA receptors, and thus facilitation of release by haloperidol was highly dependent on the rate and duration of stimulation of striatal dopaminergic terminals. In these neurons the feedback loop seems to act physiologically to depress the slope of the frequency‐release curve.