Effects of physostigmine and calcium on acetylcholine efflux from the hippocampus of freely moving rats as determined by in vivo microdialysis and a radioimmunoassay.
The effects varying the concentration of Ca2+ in perfused artificial cerebrospinal fluid ([Ca2+]csf) on basal acetylcholine (ACh) efflux from the hippocampus of freely moving rats, in the presence and absence of the cholinesterase (ChE) inhibitor physostigmine, were investigated using in vivo microdialysis and a highly specific radioimmunoassay for ACh. In the absence of physostigmine, basal ACh efflux was 3.4+/-0.7 pg/30 min (mean +/- SEM) at [Ca2+]csf = 1.26 mM. Stepwise increases in [Ca2+]csf elicited a gradual increase in ACh efflux that was significant at [Ca2+]csf = 5.04 mM. Inhibition of ChE by addition of 10 microM physostigmine to the perfusate increased the efflux of ACh to 103.2+/-21.1 pg/30 min ([Ca2+]csf = 1.26 mM), and the efflux was augmented still further by increasing [Ca2+]csf, a change that became significant at [Ca2+]csf = 3.78. These results illustrate the sensitivity of basal ACh efflux from the hippocampus to changes in the extracellular Ca2+ concentration, and suggest that a more accurate picture of hippocampal cholinergic activity is obtained by microdialysis using normal artificial cerebrospinal fluid, under physiological conditions, rather than in the presence of a ChE inhibitor.
Fujii
T
T
Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan.
Harada
H
H
Koyama
T
T
Nakajima
Y
Y
Kawashima
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002555:Cerebrospinal Fluid / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000706:statistics & numerical data; D009068:Movement / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010830:Physostigmine / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011863:Radioimmunoassay / Q000706:statistics & numerical data; D051381:Rats; D017208:Rats, Wistar
D010830:Physostigmine; D000109:Acetylcholine; D002118:Calcium