Effects of low doses of cholinesterase inhibitors on behavioral performance of robot-tested marmosets.
To investigate at which dose levels undesirable effects started, behavioural performance and several physiological parameters were measured in marmosets (Callithrix jacchus) after soman (1.75 and 3.5 micrograms/kg), sarin (3 and 6 micrograms/kg), physostigmine (10 and 20 micrograms/kg), and pyridostigmine (200 and 400 micrograms/kg). Effects on performance were investigated with a discrete-trial, two-choice visual discrimination task and a hand-eye coordination task. The former test appeared more sensitive to disruption than the hand-eye coordination task. "Motor speed" was not disrupted by any of the four compounds. However, "choice time" as well as "no attempts" increased and were clearly more disturbed by soman and physostigmine than by sarin and pyridostigmine. All effects had disappeared after 24 h. Except for a small effect of sarin on heart rate and blood pressure, none of the cholinesterase (ChE) inhibitors affected a number of physiological parameters at behavioural effective does that caused a profound ChE inhibition in blood. Take together, these results strongly suggest that both soman and physostigmine may interfere with higher CNS functions at low dose levels. These effects may go undetected because physical signs are absent.
Wolthuis
O L
OL
TNO-Pharma, Department of Experimental Pharmacology, HV Rijswijk, The Netherlands.
Groen
B
B
Busker
R W
RW
van Helden
H P
HP
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002144:Callithrix; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002802:Cholinesterases / Q000097:blood; D004192:Discrimination, Psychological / Q000187:drug effects; D005260:Female; D008297:Male; D009042:Motivation; D009048:Motor Skills / Q000187:drug effects; D010775:Photic Stimulation; D010830:Physostigmine / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D012371:Robotics; D012727:Sex Characteristics; D012999:Soman / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D012999:Soman; D010830:Physostigmine; D002802:Cholinesterases