The acute and long-term L-DOPA effects are independent from changes in the activity of dorsal raphe serotonergic neurons in 6-OHDA lesioned rats

BACKGROUND AND PURPOSE L-DOPA is still the most efficacious pharmacological treatment for Parkinson's disease. However, in the majority of patients receiving long-term therapy with L-DOPA, its efficacy is compromised by motor complications, notably L-DOPA-induced dyskinesia. Evidence suggests that the serotonergic system is involved in the therapeutic and the side effects of L-DOPA. Here, we investigate if long-term L-DOPA treatment alters the activity of the dorsal raphe nucleus (DRN) and its responses to serotonergic drugs. EXPERIMENTAL APPROACH We measured the responses of serotonergic neurons to acute and chronic L-DOPA treatment using in vivo electrophysiological single unit-extracellular recordings in the 6-OHDA-lesion rat model of Parkinson's disease. KEY RESULTS The results showed that neither acute nor chronic L-DOPA administration (6 mg.kg(-1) s.c.) altered the properties of serotonergic-like neurons. Furthermore, no correlation was found between the activity of these neurons and the magnitude of L-DOPA-induced dyskinesia. In dyskinetic rats, the inhibitory response induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.0625-16 mu g.kg(-1), i.v.) was preserved. Nonetheless, L-DOPA impaired the ability of the serotonin reuptake inhibitor fluoxetine (0.125-8 mg.kg(-1), i.v) to inhibit DRN neuron firing rate in dyskinetic animals. CONCLUSIONS AND IMPLICATIONS Although serotonergic neurons are involved in the dopaminergic effects of L-DOPA, we provide evidence that the effect of L-DOPA is not related to changes of the activity of DRN neurons. Rather, L-DOPA might reduce the efficacy of drugs that normally enhance the extracellular levels of serotonin.