Genetic deletion of muscarinic M4 receptors is anxiolytic in the shock-probe burying model.
We used muscarinic M2 and M4 receptor knockout (KO) mice to further explore the role of the cholinergic system in anxiety. Using the shock-probe burying model we were able to both assess anxiety and cognition. In this paradigm, an anxiolytic response is reflected by decreased burying behavior. In addition, retention latency depicts long-term memory performance. Whereas muscarinic M2 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.
Degroot
Aldemar
A
Eli Lilly and Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN, 46285-0510, USA.
Nomikos
George G
GG
D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology*; D004597:Electroshock; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D043585:Receptor, Muscarinic M2 / Q000235:genetics / Q000502:physiology; D043588:Receptor, Muscarinic M4 / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
D043585:Receptor, Muscarinic M2; D043588:Receptor, Muscarinic M4