Specific Neuromodulatory Actions of Amyloid-β on Dopamine Release in Rat Nucleus Accumbens and Caudate Putamen

Abstract

We previously demonstrated that amyloid-β (Aβ) has a neuromodulatory action in the nucleus accumbens (NAc). In this area of the brain, the peptide disrupts the cholinergic control of dopamine (DA) release both in vivo and in vitro. The aim of the present work was to extend the research on the neuromodulatory effect of Aβ_1-40 on DA transmission to different release stimuli and to another dopaminergic brain area, the caudate putamen (CPu), in order to clarify whether the effect of the peptide is stimulus- or brain area-selective. We performed both in vivo (microdialysis associated to HPLC) and in vitro studies (synaptosomes in superfusion). Both in NAc and in CPu and both in vivo and in vitro, Aβ did not affect either basal or potassium-stimulated DA release. In CPu, the Aβ ability to impair the DA release evoked by the cholinergic agonist carbachol, observed in NAc, was confirmed only in vitro. Moreover, in vitro Aβ affected a specific component of the DA overflow evoked by the non-selective metabotropic glutamate receptors agonist t-ACPD. Altogether, these results show that Aβ may have different neuromodulatory actions depending upon the secretory stimulus and, in vivo, the brain area investigated.