Infralimbic muscarinic M1 receptors modulate anxiety-like behaviour and spontaneous working memory in mice

Abstract.

Rationale: Spontaneous working memory and anxiety-like behaviour can be concurrently influenced following kappa1 opioid agonist or antagonist infusions in the infralimbic (IL) area of the ventromedial prefrontal cortex (vmPFC) in CD-1 mice. Objective: The present study sought to evaluate whether acetylcholine (ACh) muscarinic (M) receptor drugs can similarly influence these cognitive-behavioural processes in the IL cortex. Method: Anxiety was evaluated in the elevated plus-maze and spontaneous working memory was evaluated in the Y-maze following scopolamine, pirenzepine or McN-A-343 infusion in the IL cortex. Results: In experiment 1, the non-specific muscarinic receptor antagonist, scopolamine, was anxiogenic in trial 1 (5, 10 and 20 nmol), but did not influence behaviour in trial 2 (no-injection) in the elevated plus-maze 24 h later. In week 2, scopolamine disrupted spontaneous working memory in the Y-maze at the highest dose (20 nmol). In experiment 2, pretreatment with the M1 antagonist, pirenzepine, was anxiolytic in trial 1 (5 and 10 nmol), as well as in trial 2 (no-injection) in the elevated plus-maze 24 h later (0.25, 1.25, 2.5, 5 and 10 nmol). In week 2, pirenzepine disrupted spontaneous working memory in the Y-maze (2.5, 5 and 10 nmol). In experiment 3, pretreatment with the M1 agonist, McN-A-343, was anxiogenic in trial 1 (2.5, 5, 10 and 20 nmol), as well as in trial 2 (no-injection) in the elevated plus-maze 24 h later (2.5, 5, 10 and 20 nmol). In week 2, McN-A-343 enhanced spontaneous working memory in the Y-maze (2.5, 5, 10 and 20 nmol). Conclusions: (1) Enhanced ACh transmission in the vmPFC induces anxiety in challenging environments and enhances spontaneous working memory performance. (2) Blocking or activating postsynaptic M1 receptors in the vmPFC may truncate or exaggerate, respectively, afferent anxiety-relevant information. (3) IL pirenzepine and McN-A-343 exert long-term opposite effects on aversive learning during trial 1 in the elevated plus-maze.