Aims: 

Viability of the mice with no acetylcholinesterase (AChE-/-) is achieved by many adaptation changes, among which down-regulation of muscarinic receptors (MR) in the brain and periphery was described. We hypothesize that in accordance to maintain neurotransmitter balance, the AChE-/- brain has decreased dopaminergic receptors (DR).

Methods: 

(1) DR in the striatum of adult wild-type and AChE-/- mice were quantified by radioligand binding, using specific ligands for D1- and D2-like DR. (2) The results were confirmed by immunohistochemistry, using primary anti-D1A and anti-D2 antibodies. (3) Striatal sections were stained with DNA-specific dye. (4) cAMP contents were measured using an immunoassay kit. (5) PI-PLC activity was measured in striatal homogenates with radiolabeled PIP2 substrate.

Results: 

KD and B _max values obtained in wild-type mouse for both D1-like and D2-like receptor ligands correlated with values published by other authors. The D1-like DR in AChE-/- striatum were reduced to 5% of normal. D2-like DR in the AChE-/- striatum were almost undetectable under our conditions. These results were confirmed by immunohistochemistry. DNA-specific staining in the striata did not differ in size, density and distribution between the two genotypes. PI-PLC activity did not differ in the mutant striata comparing to wt.

Conclusion: 

Results suggest severe alteration of the dopamine pathway in AChE-/- striatum without changes in the neuronal density. This is accompanied by 40 to 64% reduction in MR. We conclude that the lower binding of the specific ligands in both systems must be caused by the decreased number of the receptors on the cell surface.