Dopamine modulates cholinergic cortical excitability in Alzheimer's disease patients.
In Alzheimer's disease (AD) patients dysfunction of cholinergic neurons is considered a typical hallmark, leading to a rationale for the pharmacological treatment in use based on drugs that enhance acetylcholine neurotransmission. However, besides altered acetylcholine transmission, other neurotransmitter systems are involved in cognitive dysfunction leading to dementia. Among others, dopamine seems to be particularly involved in the regulation of cognitive processes, also having functional relationship with acetylcholine. To test whether cholinergic dysfunction can be modified by dopamine, we used short latency afferent inhibition (SLAI) as a neurophysiological tool. First, we tested the function of the cholinergic system in AD patients and in healthy subjects. Then, we tested whether a single L-dopa challenge was able to interfere with this system in both groups. We observed that SLAI was reduced in AD patients, and preserved in normal subjects. L-dopa administration was able to restore SLAI modification only in AD, having no effect in healthy subjects. We conclude that dopamine can modify SLAI in AD, thus confirming the relationship between acetylcholine and dopamine systems. Moreover, it is suggested that together with cholinergic, dopaminergic system alteration is likely to occur in AD, also. These alterations might be responsible, at least in part, for the progressive cognitive decline observed in AD patients.
Martorana
Alessandro
A
Clinica Neurologica, Dipartimento di Neuroscienze, Università di Roma Tor Vergata, Roma, Italy. martorana@med.uniroma2.it
Mori
Francesco
F
Esposito
Zaira
Z
Kusayanagi
Hajime
H
Monteleone
Fabrizia
F
Codecà
Claudia
C
Sancesario
Giuseppe
G
Bernardi
Giorgio
G
Koch
Giacomo
G
D000109:Acetylcholine / Q000378:metabolism*; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000494:pharmacology* / Q000627:therapeutic use; D015259:Dopamine Agents / Q000494:pharmacology / Q000627:therapeutic use; D004558:Electric Stimulation / Q000379:methods; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013223:Statistics as Topic; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation / Q000379:methods
D015259:Dopamine Agents; D007980:Levodopa; D000109:Acetylcholine; D004298:Dopamine