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Reversal of both QNX‐induced locomotion and habituation decrement is indicative of M 1 agonist properties
Author(s) -
Carlezon William A.,
Cornfeldt Michael L.,
Szewczak Mark R.,
Fielding Stuart,
Dunn Robert W.
Publication year - 1991
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430230406
Subject(s) - habituation , agonist , oxotremorine , antagonist , physostigmine , chemistry , cholinergic , muscarinic acetylcholine receptor , endocrinology , medicine , pharmacology , receptor , psychology , neuroscience
Scopolamine, a non‐selective muscarinic antagonist at M 1 and M 2 receptors, has been shown to cause hyperactivity and memory deficits in rodents. However, the relative role of activation at M 1 and M 2 receptors is unclear. The effects in rats of a putative M 1 antagonist 3‐quinuclidinyl‐xanthene‐9‐carboxylate hemioxalate hydrate (QNX) were assessed in a paradigm that measures locomotion and habituation, a form of non‐associative learning, to a locomotor activity box. On day 1, subcutaneous administration of QNX (1.0 mg/kg) elicited a large (370%) increase in locomotion. On day 2, control animals demonstrated habituation 24 hr after their first exposure to the locomotor box, as shown by significant decreases (−47%) in locomotor activity, while on day 2 the locomotor activity scores of animals that had been treated on the previous day with QNX did not differ from the day 1 scores of control animals. The selective M 1 agonist 4‐(m‐chlorophenylcarbamoyloxy)‐2‐butynyl‐trimethyl ammonium chloride (McN‐A‐343, 10.0 mg/kg) significantly attenuated both the QNX‐induced locomotion and habituation deficit, while neither the non‐selective muscarinic agonist oxotremorine (0.125 mg/kg) nor the acetylcholinesterase inhibitor physostigmine (0.06 mg/kg) had a significant effect on these behaviors. These data suggest that, in this model, the M 1 cholinergic receptor mediates both locomotion and habituation. Furthermore, M 1 agonists can be identified by reversal of both QNX‐induced locomotion and memory decrement in this paradigm.