The 5-HT4 agonist prucalopride stimulates L-DOPA-induced dopamine release in restricted brain regions of the hemiparkinsonian rat in vivo

Abstract

The efficacy of L-3,4-dihydroxyphenylalanine (L-DOPA) in the treatment of Parkinson’s disease (PD) is impaired by anxiety or depression in some patients and iatrogenic side effects such as dyskinesia. Classical pharmacological tools such as selective serotonin reuptake inhibitors could be interesting to limit motor or nonmotor undesirable effects, but they directly target the activity of serotonergic neurons. Indeed, serotonergic (5-HT) neurons are responsible for L-DOPA-induced dopamine (DA) release and some of the inherent behavioral effects at the expense of 5-HT itself. Therefore, the difficulty emerging with the therapies associated with L-DOPA is to enhance central DA tone, without further alteration of 5-HT transmission and excessive striatal DA tone correlated to the possible appearance of dyskinesia.