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Decreased striatal release of acetylcholine following withdrawal from long-term treatment with haloperidol: Modulation by cholinergic, dopamine-D 1 and -D 2 mechanisms
Journal article   Peer reviewed

Decreased striatal release of acetylcholine following withdrawal from long-term treatment with haloperidol: Modulation by cholinergic, dopamine-D 1 and -D 2 mechanisms

E. Friedman, H.Y. Wang and P. Butkerait
Neuropharmacology, v 29(6), pp 537-544
1990
DOI: https://doi.org/10.1016/0028-3908(90)90065-Y
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Abstract

acetylcholine release chronic haloperidol dopamine receptors muscarinic autoreceptors striatum tardive dyskinesia
The effect of chronic treatment with haloperidol (2.7–5.3 μmol/kg/day) on K +-evoked release of [ 3H] acetylcholine (ACh) from superfused slices of the striatum was assessed. Acute injections of haloperidol (0.7–13.3 μmol/kg) produced 5–54% increases in the release of [ 3H]ACh in the striatum. Chronic treatment with haloperidol for 2.5 and 5 months also resulted in enhanced release of [ 3H]ACh in the striatum (28–35%). However, withdrawal from 2.5 and 5 months of treatment produced 34 and 38% decreases in K +-evoked release of [ 3H]ACh in the striatum, respectively. The drug SKF 38393 (D 1-agonist), produced concentration-dependent (0.1–10 μM) increases (24–59%) in the release of [ 3H]ACh in the striatum which were blocked by the selective D 1-antagonist, SCH 23390. The effect of stimulation of D 1-receptors was significantly reduced after 2.5 or 5 months of chronic treatment with haloperidol. Both LY 171555 (D 2-agonist) and carbachol (muscarinic agonist) produced concentration-dependent (0.1–10 μM) inhibitions of the release of [ 3H]ACh in the striatum (LY171555: 28–62%; carbachol: 23–63%). Long-term treatment with haloperidol (2.5 and 5 months) elicited increases in sensitivity to the effect of LY171555, while the effect of carbachol was diminished only after the 5-month treatment period. These findings demonstrate that withdrawal from chronic exposure to haloperidol in the rat results in a reduction in the release of acetylcholine in the striatum. This effect is accompanied by (1) attenuated dopaminergic D 1 mechanisms which ordinarily facilitate evoked release of ACh, (2) enhanced D 2 mechanism which elicits inhibition of the release of ACh in the striatum, and (3) diminished muscarinic inhibitory influence which regulates the release of ACh.

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