Genetic deletion of muscarinic M4 receptors is anxiolytic in the shock-probe burying model

We used muscarinic M-2 and M-4 receptor knockout (KO) mice to further explore the role of the cholinergic system in anxiety. Using the shockprobe burying model we were able to both assess anxiety and cognition. In this paradigm, ail anxiolytic response is reflected by decreased burying behavior. In addition, retention latency depicts long-term memory performance. Whereas muscarinic M, receptor KO mice did not differ behaviorally from wild-type mice, muscarinic M4 receptor KO mice showed increased anxiolysis, but normal long-term memory compared to wild-type mice. Therefore, muscarinic M4 receptors are of particular significance in anxiety modulation that seems dissociated from changes in long-term memory. (c) 2005 Elsevier B.V All rights reserved.