Effect of intrastriatal injection of diisopropylfluorophosphate on acetylcholine, dopamine, and serotonin metabolism.

Diisopropylfluorophosphate (81.5 nmol) was injected directly into the striata of rats to study changes in striatal metabolism of acetylcholine (ACh), 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (serotonin) at early time points following acute irreversible inhibition of cholinesterase. Twenty minutes following the intrastriatal injection of diisopropylfluorophosphate, levels of striatal acetylcholine were elevated by 50%, but a decrease in KACh compensated for this change. At 1 h, levels of ACh were still elevated, but not significantly different from control values. However, KACh and, hence, ACh turnover were greatly enhanced at this time. Finally, at 24 h, striatal ACh content was only slightly elevated and KACh and the turnover rate of ACh had returned to control values. Striatal cholinesterase activity remained significantly inhibited at all three times. At none of these times was ACh content or turnover affected in the parietal cortex, hippocampus, hypothalamus, or medulla/pons. Neither dopamine and its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid nor serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly affected at any of the three times by intrastriatal diisopropylfluorophosphate treatment. Possible mechanisms of the changes in cholinergic parameters are discussed.