Brain regional distribution of physostigmine and its relation to cerebral blood flow following intravenous administration in rats

Abstract

3H-labeled physostigmine (50 micrograms.kg-1) was administered intravenously to rats, and its concentration in brain tissue and spinal cord was assessed by quantitative autoradiography. Regional cerebral blood flow (rCBF) was measured with iodo-14C-antipyrine autoradiography in control rats and in animals injected i.v. with a dose of physostigmine similar to that used for the distribution studies. Tissue concentration of 3H-physostigmine was correlated with rCBF for 37 brain regions. A high degree of correlation was found at 0.5 min after drug injection, r (correlation coefficient) = 0.87. This association decreased at later times (5 min r = 0.73, 12 min r = 0.24). Structures with high cholinesterase activity (caudate-putamen, amygdala, hippocampus) showed greater retention of physostigmine over time. The highest initial physostigmine concentrations were found in regions lacking a blood-brain barrier (pineal bland, median eminence, choroid plexus) (range = 10.4-23.8 nCi/mg) and the lowest in white matter (corpus callosum, internal capsule, hippocampus commisure, spinal cord dorsal column) (range = 1.2-2.6 nCi/mg). Initial concentrations of the drug in the areas in which physostigmine induced vasodilatation (motor, sensory, temporal and occipital cortex, claustrum, and superior collicullus) were not different from concentrations in areas of comparable basal rCBF in which no such effect was observed. Variations in drug access to brain regions, then, do not explain the topographical variations of the cerebrovascular action of physostigmine.

Effects of Ovariectomy on Cerebral Blood Flow of Rats

“…We followed the protocol described by Sakurada et al [13] with a modification to euthanize the animals by intravenous injection [14, 15, 16, 17, 18] rather than decapitation as originally described. Iodo- 14 C-antipyrine autoradiography offers quantitative measurements of CBF in units of milliliters of blood per gram of tissue per minute allowing comparisons among different animals, not just changes over controls in single animals like other techniques presently in use (i.e.…”

Heptyl‐physostigmine enhances basal forebrain control of cortical cerebral blood flow

“…Indeed, physostigmine also elevates both resting and BF-elicited increases in cortical CBF (Arneric, 1988;Scremin et al, 1988;Lacombe et al, 1989). However, distribution studies indicate that in various cortical regions the tissue half-lives range from 5 to 10 min (Scremin et al, 1990), while CBF studies suggest that the effects on the cerebral circulation have a half-life of 10-15 min (Arneric, 1988;Scremin et al, 1988). The slower onset to maximal CBF response for H-PHY (> 15 min) compared to physostigmine can be accounted for by route of administration (i.m.…”

Hypnotizability-Related Cerebral Blood Flow

“…The hypothesis that the artery dilation may be mediated by a decreased pH in the extracellular fluid, as CO2 freely diffuses across the cerebrovascular endothelium, is contradicted by experiments reporting the effects of blockade of the cerebrovascular action of CO2 by brainstem lesions [25,26] or decerebration [27][28][29], cholinergic blockers [30][31][32][33], inhibitors of prostaglandin [34,35] and NO synthesis [36].…”