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‐HT(1A) receptor agonist 8‐OH‐DPAT (0.0625–16 μg·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. LINKED ARTICLES: This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc