The behavioral effects of heptyl physostigmine, a new cholinesterase inhibitor, in tests of long-term and working memory in rodents.
We assessed the effects of heptyl physostigmine, a new cholinesterase inhibitor, in a mouse tail-flick (TF) test, a mouse and rat passive avoidance test, a rat conditioned suppression-of-drinking (CSD) test, a rat Random Interval (RI) response rate test and a rat delayed matching-to-position (DMTP) test. In the TF test, a dose of 8.0 mg/kg of heptyl induced a significant antinociceptive effect that was in excess of 75% of the maximum possible effect 300 minutes after administration. In the mouse passive avoidance test, a dose of 3.0 mg/kg of heptyl fully reversed, and a dose of 1.0 mg/kg partially reversed, a scopolamine-induced (0.2 mg/kg) deficit. In the rat passive avoidance test, a dose of 8.0 mg/kg fully reversed a scopolamine-induced (0.2 mg/kg) deficit, while a dose of 4.0 mg/kg of heptyl was without effect. In the same experiment, a dose of 0.6 mg/kg of physostigmine partially reversed the scopolamine-induced deficit. In the CSD test, a dose of 8.0 mg/kg of heptyl fully reversed, and doses of 1.0 and 4.0 mg/kg of heptyl partially reversed, the deficit induced by scopolamine (0.4 mg/kg). In the RI response rate test, doses of 8.0 mg/kg and 0.6 mg/kg of physostigmine fully suppressed lever pressing for food rewards. Doses of 4.0 mg/kg of heptyl and below had no effect on lever-pressing rates. In the working memory test (DMTP), 4.0 mg/kg heptyl partially reversed the scopolamine-induced deficit (0.2 mg/kg) in the number of correct choices made, but did not affect the scopolamine-induced deficit in the number of trials completed.(ABSTRACT TRUNCATED AT 250 WORDS)
Dawson
G R
GR
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Bentley
G
G
Draper
F
F
Rycroft
W
W
Iversen
S D
SD
Pagella
P G
PG
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012601:Scopolamine / Q000494:pharmacology
D000700:Analgesics; D002800:Cholinesterase Inhibitors; D010830:Physostigmine; D012601:Scopolamine