Neuronal nicotinic and muscarinic receptor subtypes at different ages of transgenic mice overexpressing human acetylcholinesterase

Abstract

Subtypes of nicotinic (alpha4 and alpha7) as well as muscarinic (M1 and M2) receptor binding sites were quantified in the brain of transgenic mice overexpressing human acetylcholinesterase (AChE) at different ages using selective radioligands. A significant increase in [(3)H]cytisine (alpha4) binding was found in the cortex and striatum of AChE transgenic (hAChE-Tg) mice from 3 days to 12 months of age in comparison to non-transgenic mice. In addition a significant increase in [(3)H]AF-DX-384 (M2) binding was found in the striatum of hAChE-Tg mice at 3 months of age compared to controls. No major alteration was observed in the [(125)I]alpha-bungarotoxin (alpha7) or the [(3)H]pirenzepine (M1) binding sites. The persistent increase in alpha4 and M2 receptor binding sites in hAChE-Tg mice suggests that these receptor subtypes may play an important role in compensatory mechanisms facilitating the impaired cholinergic neurotransmission in hAChE-Tg.