Reversal of both QNX‐induced locomotion and habituation decrement is indicative of M₁ agonist properties

Abstract

Scopolamine, a non-selective muscarinic antagonist at M, and M, receptors, has been shown to cause hyperactivity and memory deficits in rodents. However, the relative role of activation at M, and M , receptors is unclear. The effects in rats of a putative M, 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 .O 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 Mi agonist 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethyl 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 (0.1 25 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, cholinergic receptor mediates both locomotion and habituation. Furthermore, Mi agonists can be identified by reversal of both QNX-induced locomotion and memory decrement in this paradigm.