Depression‐like Symptoms are Associated with Dysbalance in Vascular Norepinephrine Uptake. This is Worsening by Antidepressants and Increases the Risk for Hypertension.

Abstract

Antidepressants affecting norepinephrine (NE) reuptake are known to increase the risk for hypertension. Anhedonia ‐ a decreased ability to experience pleasures ‐ is a central symptom in depression and can be evoked in preclinical models exploring the role of the stressful environment in mediating affective signs and autonomic function.Some rats exposed to Chronic Mild Stress (CMS) developed depression‐like symptoms (i.e. anhedonia, measured by sucrose intake) while others were resilient to 8 wks of CMS. Normal blood pressure and decreased cardiac function suggested increased peripheral resistance in rats with depression‐like symptoms. Chronic treatment with escitalopram (SSRI) did not affect blood pressure but normalized behavior in ~50% of treated rats, e.g. responders.Resistance (small mesenteric and femoral) arteries from CMS and non‐stressed rats responded similarly to NE in vitro. Inhibition of neuronal reuptake with cocaine increased NE sensitivity more in rats with depression‐like symptoms than in resilient and non‐stressed groups. Corticosterone‐sensitive extra‐neuronal catecholamine uptake was diminished in rats exposed to CMS. These changes were associated with upregulation of the neuronal NE transporter and reduced expression of the extra‐neuronal transporter (OCT‐2) in arteries from 'depressed' rats. Escitalopram further upregulated neuronal NE reuptake in all groups.Our results indicate that depression‐like symptoms are associated with changes in NE uptake in the vascular wall and could explain pro‐hypertensive action of some antidepressants.