Dataset Information

The effect of 5-HT_1A receptor agonists on the entopeduncular nucleus is modified in 6-hydroxydopamine-lesioned rats.

ABSTRACT:

Background and purpose

l-DOPA prolonged treatment leads to disabling motor complications as dyskinesia that could be decreased by drugs acting on 5-HT_1A receptors. Since the internal segment of the globus pallidus, homologous to the entopeduncular nucleus in rodents, seems to be involved in the etiopathology of l-DOPA-induced dyskinesia, we investigated whether the entopeduncular nucleus is modulated by the 5-HT_1A 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 entopeduncular nucleus 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 entopeduncular nucleus 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-HT_1A receptor antagonist, WAY-100635. Neither buspirone nor 8-OH-DPAT modified the low-frequency oscillatory activity in the entopeduncular nucleus or its synchronization with the motor cortex. Buspirone did not alter the response induced by subthalamic nucleus opto-stimulation in the entopeduncular nucleus.

Conclusion and implications

Systemic 5-HT_1A receptor activation elicits different effects on the electrophysiological properties of the entopeduncular nucleus depending on the integrity of the nigrostriatal pathway and it does not alter the relationship between subthalamic nucleus and entopeduncular nucleus neuron activity.

SUBMITTER: Vegas-Suarez S

PROVIDER: S-EPMC8252460 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIntermittent hypoxia induces increased ventilatory responses in a 5-HT-dependent manner. This study aimed to explore that effect of raphe magnus serotonin 1A receptor (5-HT1A) receptor on the increased ventilatory responses induced by intermittent hypoxia.MethodsStereotaxic surgery was performed in adult male rats, and acute and chronic intermittent hypoxia models were established after recovery from surgery. The experimental group received microinjections of 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the raphe magnus nucleus (RMg). Meanwhile, the control group received microinjections of artificial cerebrospinal fluid instead of 8-OH-DPAT. Ventilatory responses were compared among the different groups of oxygen status. 5-HT expressions in the RMg region were assessed by immunohistochemistry after chronic intermittent hypoxia.ResultsCompared with the normoxia group, the acute intermittent hypoxia group exhibited higher ventilatory responses (e.g., shorter inspiratory time and higher tidal volume, frequency of breathing, minute ventilation, and mean inspiratory flow) (P < 0.05). 8-OH-DPAT microinjection partly weakened these changes in the acute intermittent hypoxia group. Further, compared with the acute intermittent hypoxia group, rats in chronic intermittent hypoxia group exhibited higher measures of ventilatory responses after 1 day of intermittent hypoxia (P < 0.05). These effects peaked after 3 days of intermittent hypoxia treatment and then decreased gradually. Moreover, these changes were diminished in the experimental group. 5-HT expression in the RMg region increased after chronic intermittent hypoxia, which was consistent with the changing trend of ventilatory responses. While activation of the 5-HT1A receptor in the RMg region alleviated this phenomenon.ConclusionsThe results indicate that RMg 5-HT1A receptor, via changing the expression level of 5-HT in the RMg region, is involved in the modulation of the increased ventilatory responses induced by intermittent hypoxia.

Dataset Information

The effect of 5-HT_1A receptor agonists on the entopeduncular nucleus is modified in 6-hydroxydopamine-lesioned rats.

Background and purpose

Experimental approach

Key results

Conclusion and implications

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background and purpose

Experimental approach

Key results

Conclusion and implications

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

The effect of 5-HT_1A receptor agonists on the entopeduncular nucleus is modified in 6-hydroxydopamine-lesioned rats.