Pyridostigmine-induced inhibition of blood acetylcholinesterase (AChE) and resulting effects on manual ocular tracking performance in the trained baboon.
A method was developed to determine the effects of pyridostigmine on sensory-motor control in baboons trained to perform visuo-oculo-manual tracking tasks. The performance was evaluated in terms of accuracy, maximum smooth pursuit velocity, and gain. Administration of pyridostigmine (0.4-0.7 mg/kg intramuscularly) induced a dose-related decrease in smooth pursuit performance which appeared 10 to 30 min after injection and lasted about 1 h. If the animal was allowed to track the target with its hand or to move the target itself, the smooth pursuit performance increased significantly, returning to near normal values. The movement of the hand was not altered. The effect of intramuscular injections of pyridostigmine (0.5 mg/kg) was studied on blood acetylcholinesterase activity in alert baboons. Maximum inhibition of about 60% of baseline activity was observed 10 min after pyridostigmine injection. Subsequently the activity slowly tended to return to control level. Three hours after drug administration, acetylcholinesterase activity inhibition was still 34.1% of control value. In the baboon, the time-course of acetylcholinesterase activity recovery after injection is similar to that recorded in human. The similarity of the time-course of blood acetylcholinesterase activity and changes in smooth pursuit performance suggests a causal relationship between the two factors. A further experiment showed that pyridostigmine administered per os at a dose normally used as a prophylactic against organophosphates does not significantly alter sensorimotor performance as evaluated at the oculomanual tracking system level. When compared to the literature, our results suggest that the baboon can be used as a human experimental analog for pharmacological studies such as the action of acetylcholinesterase inhibitors.
Vercher
J L
JL
Université de Provence, URA CNRS 372, Marseille, France.
Dusticier
N
N
Ebihara
Y
Y
Nieoullon
A
A
Gauthier
G M
GM
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000110:Acetylcholinesterase / Q000097:blood*; D000818:Animals; D001288:Attention / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005133:Eye Movements / Q000187:drug effects*; D005260:Female; D007273:Injections, Intramuscular; D007649:Ketamine / Q000494:pharmacology; D007699:Kinesthesis / Q000187:drug effects; D008297:Male; D010215:Papio; D010830:Physostigmine / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D011698:Pursuit, Smooth / Q000187:drug effects*; D011729:Pyridostigmine Bromide / Q000494:pharmacology*
D007649:Ketamine; D010830:Physostigmine; D000110:Acetylcholinesterase; D011729:Pyridostigmine Bromide; D000109:Acetylcholine