Abstract
Background: As a test of possible muscarinic up-regulation, the cortisol response
to intravenous (IV) physostigmine (an anticholinesterase) was measured in 9 elderly
volunteers before and after chronic cholinergic blockade with the muscarinic cholinergic
antagonist scopolamine.
Methods: Each of the 9 elderly control subjects was given two physostigmine (0.5 mg
IV) infusions separated by 21 doses of nightly scopolamine (1.2 mg p.o.). No scopolamine
was administered the night before infusions, and glycopyrrolate (0.2 mg IV) was administered
prior to physostigmine to block its peripheral effects. Vital signs were monitored
and blood samples were collected at six time points surrounding the physostigmine
infusion (−10, +10, +20, +30, +50, and +70 min). Behavioral measures and cognitive
tests were administered prior to and 30 min after the physostigmine.
Results: The cortisol response to physostigmine was greater after the second (post-chronic
scopolamine) infusion study compared to the first (p < .05) as measured by an area under the curve analysis of all time points. When individual
time points were compared, the mean cortisol response was significantly increased
after the second physostigmine infusion at the +50- and +70-min time points (p < .05). There were no significant changes in behavioral rating scales, cognitive
tests, or vital signs between the two physostigmine infusion study days.
Conclusions: This study demonstrates increased hypothalamic–pituitary–adrenocortical
axis responsivity to a central nervous system cholinergic stimulus after chronic muscarinic
blockade in 9 elderly control subjects. It also gives further evidence to support
previous suggestions of muscarinic plasticity, specifically postsynaptic up-regulation,
in the aging brain following exposure to chronic anticholinergic treatment.
Keywords
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Article info
Publication history
Accepted:
September 1,
1998
Received in revised form:
August 13,
1998
Received:
March 9,
1998
Identification
Copyright
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
