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

Rationale: Spontaneous working memory and anxiety-like behaviour can be con currently influenced following kappal opioid agonist or antagonist infusion s in the infralimbic (IL) area of the ventromedial prefrontal cortex (vmPFC ) in CD-1 mice. Objective: The present study sought to evaluate whether ace tylcholine (ACh) muscarinic (M) receptor drugs can similarly influence thes e cognitive-behavioural processes in the IL cortex. Method: Anxiety was eva luated in the elevated plus-maze and spontaneous working memory was evaluat ed in the Y-maze following scopolamine, pirenzepine or McN-A-343 infusion i n the IL cortex. Results: In experiment 1, the non-specific muscarinic rece ptor 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, pretr eatment with the M1 antagonist, pirenzepine, was anxiolytic in trial 1 (5 a nd 10 nmol), as well as in trial 2 (no-injection) in the elevated plus-maze 24 h late (0.25, 1.25, 2.5, 5 and 10 nmol). In week 2, pirenzepine disrupt ed spontaneous working memory in the Y-maze (2.5, 5 and 10 nmol). In experi ment 3, pretreatment with the M1 agonist, McN-A-343, was anxiogenic in tria l 1 (2.5, 5, 10 and 20 nmol), as well as in trial 2 (no-injection) in the e levated 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 i n challenging environments and enhances spontaneous working memory performa nce. (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 aver sive learning during trial 1 in the elevated plus-maze.