Cardiovascular effects of early maternal separation and escitalopram treatment in rats with depressive-like behaviour

Auton Neurosci. 2024 Dec:256:103223. doi: 10.1016/j.autneu.2024.103223. Epub 2024 Nov 27.

Abstract

Depression and cardiovascular diseases are two of the world's major health problems. Escitalopram (ESC) is widely used because of its safety in relation to other drugs in that class; however, it can affect the cardiovascular system. The present study evaluated the cardiovascular parameters of depressive-like male rats and the cardiovascular effects of ESC treatment on that condition. The EMS protocol consisted of separating the litter from the dam for 3 h over 13 days. Animals were anesthetized with tribromoethanol (250 mg/kg, intraperitoneally) and the catheters were inserted into the femoral and into the femoral vein. Depressive-like rats showed an increase in the pressor response to phenylephrine (Emax:depressive = 50.36 ± 2.997 mmHg; non-depressive = 39.51 ± 3.328 mmHg; p < 0.05) and a reduction in the EC50 (depressive = 0.6203 ± 0.03005 μg/kg; non-depressive = 0.7320 ± 0.03519 μg/kg; p < 0.05) with no change in the other cardiovascular parameters. After treatment with ESC, a reduction of intrinsic heart rate was observed in the depressive-like rats (control: 342 ± 6 bpm; ESC: 316 ± 5 bpm; p < 0.05). In addition, ESC treatment increased the bradycardic (control: -97.81 ± 8.3 bpm; ESC: -137.1 ± 12.31 bpm; p = 0.0236; t = 2.502) during the baroreflex response, caused by an increase in cardiac parasympathetic modulation in the heart, in depressive-like rats (p < 0.001). The findings suggest that depressive-like rats showed cardiovascular changes, and that ESC treatment was able to reverse these changes, suggesting that ESC has a good safety profile for depressive patients with cardiovascular disease due to increased parasympathetic modulation.

Keywords: Cardiovascular safety; Depression; Depressive-like behaviour; Selective serotonin reuptake inhibitor.

MeSH terms

  • Animals
  • Antidepressive Agents, Second-Generation / pharmacology
  • Baroreflex / drug effects
  • Baroreflex / physiology
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Citalopram / pharmacology
  • Depression* / drug therapy
  • Depression* / physiopathology
  • Disease Models, Animal
  • Escitalopram* / pharmacology
  • Female
  • Heart Rate* / drug effects
  • Male
  • Maternal Deprivation*
  • Phenylephrine / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Escitalopram
  • Phenylephrine
  • Antidepressive Agents, Second-Generation
  • Citalopram