Specific neuromodulatory actions of amyloid-beta on dopamine release in rat nucleus accumbens and caudate putamen.
We previously demonstrated that amyloid-beta (Abeta) 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 Abeta (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, Abeta did not affect either basal or potassium-stimulated DA release. In CPu, the Abeta ability to impair the DA release evoked by the cholinergic agonist carbachol, observed in NAc, was confirmed only in vitro. Moreover, in vitro Abeta affected a specific component of the DA overflow evoked by the non-selective metabotropic glutamate receptors agonist t-ACPD. Altogether, these results show that Abeta may have different neuromodulatory actions depending upon the secretory stimulus and, in vivo, the brain area investigated.
Department of Experimental and Applied Pharmacology, University of Pavia, Pavia, Italy.
Elisa
E
Mura
Stefania
S
Preda
Stefano
S
Govoni
Cristina
C
Lanni
Luigia
L
Trabace
Massimo
M
Grilli
Federica
F
Lagomarsino
Anna
A
Pittaluga
Mario
M
Marchi
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002421:Caudate Nucleus / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008297:Male; D009411:Nerve Endings / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism*; D011188:Potassium / Q000502:physiology; D011699:Putamen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000502:physiology
D016229:Amyloid beta-Peptides; D011188:Potassium; D004298:Dopamine