Modulation of behavioral phenotypes by a muscarinic M1 antagonist in a @entity19 model of XXXX .

@entity410 @entity34141 @entity19 @entity37419 @entity57115 @entity2100 @entity934
RATIONALE: Muscarinic @entity934 receptors (mAChR) are G protein-coupled receptors, widely expressed in the CNS. Electrophysiological and molecular studies have provided evidence for overactive M1 receptor signaling in the @entity2100 knockout ( @entity34141 KO) @entity19 model, suggesting the involvement of the M1 receptors in @entity2100 . Overactive signaling through the M1 receptor has been hypothesized to contribute to the phenotypes seen in @entity2100 @entity19 . OBJECTIVE: We investigated the modulation of behavioral responses in the @entity34141 KO animals by reducing the activity through the muscarinic M1 receptor using the pharmacological agent @entity37419 , an M1 antagonist. METHODS: The behavioral assays used to investigate the pharmacological effects include marble burying (perseverative behavior), open-field exploration (activity), passive avoidance (learning and memory), prepulse inhibition (sensorimotor gating), and @entity410 . RESULTS: Data from the marble-burying assay suggests that treatment with @entity37419 results in a decrease in the number of marbles buried in the wild-type and in the KO animals. To examine the possibility of drug-induced sedation, overall activity was measured in an open-field chamber. @entity37419 only increases activity at a dose of 20  mg/kg in the wild-type @entity19 but did not affect exploration in the KO animals. Lastly, we observed that @entity37419 causes a significant decrease in the percentage of @entity410 in the @entity34141 KO animals. CONCLUSION: Our findings suggest that pharmacologically reducing the activity through the @entity57115 alters select behavioral responses in the @entity34141 KO @entity19 .
