Drastic decrease in dopamine receptor levels in the striatum of acetylcholinesterase knock-out mouse.
BACKGROUND
The acetylcholinesterase knock-out mouse lives to adulthood despite 60-fold elevated acetylcholine concentrations in the brain that are lethal to wild-type animals. Part of its mechanism of survival is a 50% decrease in muscarinic and nicotinic receptors and a 50% decrease in adrenoceptor levels.


OBJECTIVE
The hypothesis was tested that the dopaminergic neuronal system had also adapted.


METHODS
Radioligand binding assays measured dopamine receptor level and binding affinity in the striatum. Immunohistochemistry of brain sections with specific antibodies visualized dopamine transporter. Effects on the intracellular compartment were measured as cAMP content, PI-phospholipase C activity.


RESULTS
Dopamine receptor levels were decreased 28-fold for the D(1)-like, and more than 37-fold for the D(2)-like receptors, though binding affinity was normal. Despite these huge changes in receptor levels, dopamine transporter levels were not affected. The intracellular compartment had normal levels of cAMP and PI-phospholipase C activity.


CONCLUSIONS
Survival of the acetylcholinesterase knock-out mouse could be linked to adaptation of many neuronal systems during development including the cholinergic, adrenergic and dopaminergic. These adaptations balance the overstimulation of cholinergic receptors caused by high acetylcholine concentrations and thus maintain homeostasis inside the cell, allowing the animal to live.
Hrabovska
Anna
A
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia. anna.hrabovska@gmail.com
Farar
Vladimir
V
Bernard
Veronique
V
Duysen
Ellen G
EG
Brabec
Jiri
J
Lockridge
Oksana
O
Myslivecek
Jaromir
J
D000110:Acetylcholinesterase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011941:Receptors, Adrenergic / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D000242:Cyclic AMP; D000110:Acetylcholinesterase; D010738:Type C Phospholipases