A comparison of the effects of the novel muscarinic receptor agonists L-689,660 and AF102B in tests of reference and working memory.
Four experiments compared the CNS effects of a novel M1/M3 receptor agonist L-689,660 with those of the M1/M3 muscarinic receptor agonist AF102B. In the mouse tail-flick test of antinociception (TF) the minimum effective doses to increase tail-flick latency (MED) of L-689,660 and AF102B were 0.03 mg/kg and 10.0 mg/kg, respectively. In a rat conditioned-suppression-of-drinking (CSD) test of reference memory, doses of 0.3 and 1.0 mg/kg L-689,660 and a dose of 5.0 mg/kg AF102B reversed a scopolamine-induced deficit in performance (0.6 mg/kg). Although there was a tendency for L-689,660 to reverse the scopolamine-induced (0.4 mg/kg) performance deficit in a rat delayed-matching-to-position (DMTP) test, the difference failed to reach statistical significance. In contrast, a 5.0 mg/kg dose of AF102B potentiated the scopolamine-induced deficit in choice accuracy and the number of trials completed on this task. In a response sensitivity (RS) test, chain-pulling rates were significantly decreased by L-689,660 (MED = 0.03 mg/kg) and by AF102B (MED = 5.0 mg/kg). These results suggest that L-689,660 and AF102B may ameliorate or reverse a scopolamine-induced deficit, but only at doses that also reduce chain-pulling rates on operant schedules of reinforcement.
Dawson
G R
GR
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Bayley
P
P
Channell
S
S
Iversen
S D
SD
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003216:Conditioning, Operant / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D010277:Parasympathomimetics / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012601:Scopolamine / Q000494:pharmacology; D013876:Thiophenes
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018721:Muscarinic Agonists; D010277:Parasympathomimetics; D011719:Pyrazines; D011812:Quinuclidines; D013876:Thiophenes; C076265:L 689660; D012601:Scopolamine; C059240:cevimeline