Behavioural brain research
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The G-protein coupled muscarinic acetylcholine receptors, widely expressed in the CNS, have been implicated in fragile X syndrome (FXS). Recent studies have reported an overactive signaling through the muscarinic receptors in the Fmr1KO mouse model. Hence, it was hypothesized that reducing muscarinic signaling might modulate behavioral phenotypes in the Fmr1KO mice. Pharmacological studies from our lab have provided evidence for this hypothesis, with subtype-preferring muscarinic M1 and M4 receptor antagonists modulating select behaviors in the Fmr1KO mice. Since the pharmacological antagonists were not highly specific, we investigated the specific role of M4 receptors in the Fmr1KO mouse model, using a genetic approach. ⋯ Reducing M4 receptor signaling altered only select behavioral phenotypes in the Fmr1KO mouse model, suggesting that other targets are involved in the modulation of fragile X behaviors.
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Bile duct ligation (BDL) induces primary biliary cirrhosis characterized by cholestasis, impaired liver function and cognition including impairment of memory formation and anxiety-like behaviors. Endogenous opioid and acetylcholine levels are elevated in animal model of cholestasis. In addition, there is no data about the effects of interaction opioidergic and cholinergic systems of dorsal hippocampus (CA1) on amnesia-induced by cholestasis. ⋯ Further, all cross co-administration ineffective doses of naloxone (0.0125 μg/mice), mecamylamine (0.125 μg/mice) and scopolamine (0.125 μg/mice) reversed cholestasis-induced amnesia. All doses of the drugs have no effect on exploratory behaviors. The data strongly revealed that synergistic effect between opioidergic and cholinergic systems of CA1 on the modulation of cholestasis-induced amnesia.