P005 Neuromodulatory actions of beta-amyloid 1-40 on the muscarinic receptors which modulate the release of ACh, GABA and DA from isolated nerve endings in the rat nucleus accumbens

The neuromodulatory effect of beta-amyloid (Aβ) on the dopamine (DA) release evoked by different cholinergic stimuli was studied in the rat nucleus accumbens using in vivo the microdialysis technique and in vitro superfused synaptosomes. In the in vivo model Aβ 1-40 disrupts the cholinergic control of DA release acting downstream of the muscarinic cholinergic receptors, in particular inhibiting the protein kinase C (PKC; Preda et al., 2008). Using superfused synaptosomes we here examined the effects of Aβ 1-40 on the function of four different presynap- tic mAChR subtypes which modulate the release of ACh (M2 inhibitory autoreceptor), of GABA (M3 excitatory and M4 inhibitory mAChRs)and of DA (M5 excitatory mAChR). Our results provide the direct demonstration that Aβ1-40 (0.1 µM) can selectively inhibit the function of the mAChRs which are able to stimulate presynaptically neurotransmitter release (mAChR: M3, and M5) and not of those which modulate negatively the stimulated release (mAChR : M2 and M4).