Antagonism of muscarinic M1 receptors by dicyclomine inhibits the consolidation of morphine-associated contextual memory.

M1 muscarinic receptor has been shown to be involved in cognitive functions of the brain. Conditioned place preference (CPP) paradigm involves memory for the association between environmental stimuli and the rewarding properties produced by a treatment. Using a balanced CPP design, we studied the possible involvement of M1 muscarinic receptors on the acquisition, expression and consolidation of morphine place conditioning in male mice. Subcutaneous administration of morphine sulphate-induced CPP in a dose-dependent manner. Using a 6-day schedule of conditioning, it was found that dicyclomine, an M1 muscarinic antagonist, significantly reduced the time spent by mice in the morphine compartment when given immediately, but not 6h, after each conditioning session (consolidation). It had no effect when administered 30 min before each conditioning session during CPP training period (acquisition) or 30 min before testing for place preference in the absence of morphine (expression). It is concluded that M1 muscarinic receptors may play a time-dependent role in the consolidation of reward-related memory of morphine.