The effect of 5‐HT1A receptor agonists on the entopeduncular nucleus is modified in 6‐hydroxydopamine‐lesioned rats

L-DOPA prolonged treatment leads to disabling motor complications as dyskinesia that could be decreased by drugs acting on 5-HT1A receptors. Since the internal segment of the globus pallidus, homologous to the entopeduncular nucleus (EP) in rodents, seems to be involved in the etiopathology of L-DOPA-induced dyskinesia, we investigated whether the EP is modulated by the 5-HT1A receptor partial and full agonists, buspirone, and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) in control and 6-hydroxydopamine (6-OHDA)-lesioned rats with or without long-term L-DOPA treatment. EXPERIMENTAL APPROACH Extracellular single-unit electrocorticogram and local field potential recordings under anaesthesia, immunostaining assays and optogenetic manipulation coupled to electrophysiological recordings were performed. KEY RESULTS Systemic buspirone reduced the EP firing rate in the sham animals and burst activity in the 6-OHDA-lesioned rats (with or without L-DOPA treatment), while local administration reduced EP activity in all the groups, regardless of DA integrity. Systemic 8-OH-DPAT also induced inhibitory effects only in the sham animals. Effects triggered by buspirone and 8-OH-DPAT were reversed by the 5-HT1A receptor antagonist, WAY-100635. Neither buspirone nor 8-OH-DPAT modified the low-frequency oscillatory activity in the EP or its synchronization with the motor cortex. Buspirone did not alter the response induced by STN opto-stimulation in the EP. CONCLUSIONS AND IMPLICATIONS Systemic 5-HT1A receptor activation elicits different effects on the electrophysiological properties of the EP depending on the integrity of the nigrostriatal pathway, and it does not alter the relationship between STN and EP neuron activity.