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Intravenous physostigmine increases cerebrospinal fluid neuropeptide-Y.
W H Berrettini1, N A Garrick, J I Nurnberger
1Clinical Neurogenetics Branch, NIMH, Bethesda, MD 20892-1000.
Biological Psychiatry
|October 1, 1989
Summary
Physostigmine infusion increased cerebrospinal fluid (CSF) neuropeptide-Y (NPY) levels in both monkeys and humans. This finding suggests a new method for measuring central nervous system (CNS) responses in psychiatric research.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatric Research
Background:
- Measuring central nervous system (CNS) neurotransmitter changes after pharmacological challenges is crucial for psychiatric research.
- Cerebrospinal fluid (CSF) analysis offers a direct method to assess CNS responses.
Purpose of the Study:
- To investigate changes in CSF neuropeptide levels following physostigmine administration.
- To evaluate the potential of using CSF neuropeptide responses to pharmacological challenges as a clinical tool.
Main Methods:
- Rhesus monkeys with CSF catheters received physostigmine infusions, with serial CSF samples collected.
- Human subjects received intravenous physostigmine infusions at varying doses (0, 5, 15 µg/kg), with CSF sampled at multiple time points.
- CSF neuropeptide levels, particularly neuropeptide-Y (NPY), were analyzed.
Main Results:
- Five out of six monkeys showed a significant increase (≥50%) in CSF NPY levels post-physostigmine.
- In humans, a significant dose-time interaction (p=0.04) indicated that physostigmine (15 µg/kg) increased CSF NPY levels.
- CSF levels of seven other neuropeptides remained unaffected by the physostigmine challenge.
Conclusions:
- Pharmacological challenge paradigms can be adapted to measure CSF neuropeptides.
- This approach provides a novel method for assessing CNS stimulus-induced responses.
- The findings support the utility of CSF NPY measurements in psychiatric research.