Acute and chronic acetylcholinesterase inhibition regulates in vivo the localization and abundance of muscarinic receptors m2 and m4 at the cell surface and in the cytoplasm of striatal neurons

Acetylcholinesterase inhibitors (AChE-I) of various pharmacological classes have been used to provoke acute and chronic hypercholinergy in brain. Each condition induces a dramatic decrease of the abundance of muscarinic receptors at the membrane of neurons with simultaneous increase of these receptors in the cytoplasm in association with different subcellular organelles with characteristics depending on the duration of the treatment (short-term versus long term treatment). Each condition also induces a dramatic increase of cytoplasmic receptors associated with endosomes and multivesicular bodies. Chronic treatment with MTF induces a general decrease of m4R in the striatum without modification of the mRNA level but with an exaggerated abundance of muscarinic receptors in the cytoplasm at the sites of synthesis and maturation, i.e., endoplasmic reticulum, nuclear membrane and Golgi apparatus. These results suggest that the membrane abundance and intraneuronal distribution of neurotransmitter receptors are modified following drug treatment with specificity depending on the nature and the duration of treatment.