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The ability to measure directly central nervous system (CNS) neurotransmitter changes after an acute pharmacological challenge would be a useful clinical tool in psychiatric research. As one approach to this possibility, we attempted to measure cerebrospinal fluid (CSF) neuropeptide changes produced by an intravenous infusion of the indirect cholinergic agonist physostigmine. Six rhesus monkeys, with indwelling CSF catheters, had serial CSF samples removed before and after a 15 μg/kg physostigmine infusion. Five of six monkeys studied showed at least a 50% increase in CSF neuropeptide-Y (NPY) levels. Normal human subjects (n = 27) had CSF sampled before and 15, 30, and 45 min after an acute intravenous infusion of physostigmine (either 0, 5, or 15 μg/kg). An Analysis of Variance revealed a significant (p = 0.04) dose-time interaction, suggesting that physostigmine increased CSF NPY at the 15 μg/kg dose. CSF levels of seven other neuropeptides remained unchanged. These results suggest that the pharmacological challenge paradigm can be adapted to CSF neuropeptides, providing new measures of CNS stimulus-induced response beyond the peripheral plasma determinations usually employed.
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Received in revised form: November 26, 1988
Received: August 23, 1988The authors are indebted to Alien Albright for technical assistance in performing the NPY determinations, to Thomas Tomai for the CRF assay, to Candy Davis for the SRIF assay, and to Francis Szele for assistance in obtaining the monkey CSF samples. Chris Hoban performed the Analysis of Variance statistics.
© 1989 Published by Elsevier Inc.