Inhibitory effects of sigma‐1 ligands on handling‐induced tachycardia in conscious tethered rats. (5th April 2012)

• Record Type: Journal Article
• Authors: Delaunois, Annie; De Ron, Pierrette; Detrait, Eric; Guyaux, Michel
• Is Part Of: Fundamental & clinical pharmacology. Volume 27:Number 4(2013:Aug.)
• Page Start: 354
• Page End: 363
• Publication Date: 2012-04-05
• Subjects: Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/j.1472-8206.2012.01042.x
• Languages: English
• ISSNs: 0767-3981

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>We used conscious tethered Sprague‐Dawley rats to evaluate the cardiovascular effects of four sigma‐1 (σ<sub>1</sub>) agonists and five antagonists, given alone or in combination. All drugs were administered as a single intraperitoneal dose. The agonists were given at doses reported as efficacious in rodent cognition models, while the antagonists were administered at doses neutralizing agonist effects <italic>in vivo</italic>. Systolic blood pressure (SBP) and heart rate (HR) were continuously recorded for 20 min before and 60 min postadministration. Immediately after injection, a sudden, transitory increase in HR and SBP was noted in all animals, because of the stress induced by handling. For both parameters, a peak value (ΔHR<sub>max</sub> and ΔSBP<sub>max</sub>) and an area under the curve of changes from baseline over the period 5–20 min postinjection (ΔHR_AUC<sub>5–20 min</sub> and ΔSBP_AUC<sub>5–20 min</sub>) were calculated. Three of the four σ<sub>1</sub> agonists (SKF‐10, 047, dehydroepiandrosterone (DHEAS), Compound 14) significantly reduced ΔHR_AUC<sub>5–20 min</sub> value without changing ΔHR<sub>max</sub>, while the fourth one, SA‐4503, had no significant effect. None of the antagonists (haloperidol, rimcazole, NE‐100, and BD1047) reduced, and even one (progesterone) enhanced the stress‐induced effects on HR. No changes in SBP were noted with any compound. When the antagonist NE‐100 was administered just before SKF‐10, 047, it completely reversed the inhibitory effects of the σ<sub>1</sub> agonist on HR increase. In conclusion, we demonstrated for the first time the involvement of σ<sub>1</sub> receptors in the regulation of handling‐induced tachycardia in the conscious rat. Although additional investigations are needed to fully understand this role, it might offer new therapeutic perspectives to σ<sub>1</sub> ligands in the cardiovascular sphere.</p> </abstract>