Impact of Serotonergic 5HT 1A and 5HT 2A Receptor Activation on the Respiratory Response to Hypercapnia in a Rat Model of Parkinson's Disease

• Published in: International journal of molecular sciences 2024-04, Vol.25 (8)
• Main Authors: Andrzejewski, Kryspin, Orłowska, Magdalena E, Zaremba, Małgorzata, Joniec-Maciejak, Ilona, Kaczyńska, Katarzyna
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Dopamine - metabolism; Hypercapnia - metabolism; Hypercapnia - physiopathology; Male; Norepinephrine - metabolism; Norepinephrine - pharmacology; Oxidopamine - pharmacology; Parkinson Disease - metabolism; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1A - metabolism; Receptor, Serotonin, 5-HT2A - metabolism; Respiration - drug effects; Serotonin - metabolism; Serotonin 5-HT1 Receptor Agonists - pharmacology; Serotonin 5-HT2 Receptor Agonists - pharmacology
• ISSN: 1422-0067

In Parkinson's disease (PD), along with typical motor dysfunction, abnormal breathing is present; the cause of which is not well understood. The study aimed to analyze the effects of stimulation of the serotonergic system with 5-HT and 5-HT agonists in a model of PD induced by injection of 6-hydroxydopamine (6-OHDA). To model PD, bilateral injection of 6-OHDA into both striata was performed in male Wistar rats. Respiratory disturbances in response to 7% hypercapnia (CO in O ) in the plethysmographic chamber before and after stimulation of the serotonergic system and the incidence of apnea were studied in awake rats 5 weeks after 6-OHDA or vehicle injection. Administration of 6-OHDA reduced the concentration of serotonin (5-HT), dopamine (DA) and norepinephrine (NA) in the striatum and the level of 5-HT in the brainstem of treated rats, which have been associated with decreased basal ventilation, impaired respiratory response to 7% CO and increased incidence of apnea compared to Sham-operated rats. Intraperitoneal (i.p.) injection of the 5-HT R agonist 8-OH-DPAT and 5-HT R agonist NBOH-2C-CN increased breathing during normocapnia and hypercapnia in both groups of rats. However, it restored reactivity to hypercapnia in 6-OHDA group to the level present in Sham rats. Another 5-HT R agonist TCB-2 was only effective in increasing normocapnic ventilation in 6-OHDA rats. Both the serotonergic agonists 8-OH-DPAT and NBOH-2C-CN had stronger stimulatory effects on respiration in PD rats, compensating for deficits in basal ventilation and hypercapnic respiration. We conclude that serotonergic stimulation may have a positive effect on respiratory impairments that occur in PD.