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Frequency‐Dependent Release of Acetylcholine and Dopamine From Rabbit Striatum: Its Modulation by Dopaminergic Receptors
Author(s) -
Cubeddu Luigi X.,
Hoffmann Irene S.
Publication year - 1983
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.1471-4159.1983.tb11818.x
Subject(s) - apomorphine , acetylcholine , postsynaptic potential , dopamine , stimulation , agonist , chemistry , dopamine receptor , sulpiride , endocrinology , medicine , dopaminergic , striatum , receptor , biology , biochemistry
The release of [ 3 H]dopamine (DA) and [ 14 C]acetylcholine (ACh) was monitored from single slices of the rabbit striatum. In all cases, the evoked overflow of ACh showed a higher peak and was of shorter duration than that of 3 H products. For ACh, the release per pulse showed a marked decline with increasing frequency of stimulation, whereas flat frequency‐release curves were obtained for DA. At 0.1 and 1 Hz the evoked overflows of ACh were 15 and 7 times greater, respectively, than those of DA. Haloperidol (0.03 μ M ) and sulpiride (1 μ M ) produced large increases in the evoked overflow of DA and ACh at 3 and 10 Hz; little effect was observed at lower frequencies. These results indicate that the frequency‐release curves for DA and ACh are different and that at high frequencies the slope of the curves is modified by activation of pre‐ and postsynaptic DA receptors. Apomorphine inhibited in a concentration‐dependent fashion the evoked overflow of DA and ACh; greater inhibition was obtained at lower frequencies of stimulation. At 0.3 Hz the‐ DA agonist was two times more potent in inhibiting DA than ACh overflow (IC 50 : 12.0 ± 2.2 versus 22.0 ± 2.8 n M; p < 0.01). The greater sensitivity of pre‐than postsynaptic sites to apomorphine was also seen at higher frequencies (3 Hz). Benztropine (1/μ) reduced the evoked overflow of ACh at 10 Hz, and enhanced that of 3 H products at all rates of stimulation (0.3–10 Hz). These results suggest that the release of DA and ACh is regulated by dopaminergic receptors. They also indicate that the effects of DA agonists and antagonists and of uptake inhibitors on DA and ACh release are highly dependent on the frequency of stimulation used.