Comparison of the effects of four cholinomimetic agents on cognition in primates following disruption by scopolamine or by lists of objects.
The ability of four central cholinomimetics to reverse a scopolamine-induced spatial memory impairment or to improve visual recognition memory in primates was examined. Physostigmine (0.04-0.08 mg/kg IM) fully reversed the effects of scopolamine (0.03 mg/kg). Coadministration of pilocarpine (3.0-5.0 mg/kg) caused partial reversal of the scopolamine impairment after intermediate or long retention intervals (10 or 20 s). Treatment with arecoline (0.1-1.8 mg/kg) or nicotine (1.0-2.0 mg/kg) generally did not reverse the effects of scopolamine. A task in which memory could be taxed by increasing the number of visual stimuli presented appeared more sensitive to the effects of cholinomimetics on cognition than the scopolamine reversal model. In this paradigm treatment with physostigmine (0.001, 0.01 or 0.03 mg/kg) increased choice accuracy from about 55 to 70% correct. Arecoline improved performance at one dose only (0.1 mg/kg) which also induced marked adverse side-effects (salivation and tremor). Pilocarpine improved performance in the dose range 0.125-0.35 mg/kg, but not at higher doses which also induced marked salivation. Treatment with nicotine (0.001-2.0 mg/kg tended to improve performance but this did not reach statistical significance. The relevance of these findings for studies in man and for animal models of dementia is discussed.
Rupniak
N M
NM
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Steventon
M J
MJ
Field
M J
MJ
Jennings
C A
CA
Iversen
S D
SD
D000818:Animals; D001115:Arecoline / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D004347:Drug Interactions; D008253:Macaca mulatta; D008297:Male; D008568:Memory / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology*; D013028:Space Perception / Q000187:drug effects
D010277:Parasympathomimetics; D010862:Pilocarpine; D001115:Arecoline; D009538:Nicotine; D010830:Physostigmine; D012601:Scopolamine