Sertraline, a selective serotonin reuptake inhibitor modulates extracellular noradrenaline in the rat frontal cortex

Abstract

The selective action of selective serotonergic reuptake inhibitors (SSRIs) on 5-hydroxytryptamine (5-HT) neurotransmission underlies the therapeutic effectiveness of this class of drugs. Yet there is increasing evidence that changes in extracellular 5-HT content may result in changes in the regulation of other neurotransmitter systems. The present study examines the effects of acute and chronic administration of the SSRI sertraline on release of endogenous noradrenaline (NA) in the frontal cortex and hippocampus of the rat using in vivo microdialysis. Acute administration of sertraline did not significantly alter NA release in either the cortex or the hippocampus. However, 24 h after chronic (14 days) administration of the drug (10 mg/kg i.p. once daily), NA release in the cortex but not hippocampus was significantly enhanced. The lack of an effect on NA release following a challenge with the alpha2-antagonist idazoxan suggests that chronic drug treatment has reduced the sensitivity of cortical pre-synaptic alpha2-adrenoceptors, activation of which would normally inhibit further NA release. The possible mechanisms underlying the regional specificity of the effect of chronic and not acute sertraline administration and the implications of these results for our understanding of depression are discussed.

Synergistic Effects of Olanzapine and Other Antipsychotic Agents in Combination with Fluoxetine on Norepinephrine and Dopamine Release in Rat Prefrontal Cortex

“…However, while fluoxetine treatment resulted in a sustained elevation of [NE] ex and [DA] ex in PFC, consistent with previous reports in hypothalamus (Perry and Fuller 1997) (Thomas et al 1998).…”

Behavioral Effects of Chronic Fluoxetine in BALB/cJ Mice Do Not Require Adult Hippocampal Neurogenesis or the Serotonin 1A Receptor

“…Some studies suggest that SSRIs augment noradrenergic, as well as serotonergic, function when given chronically (Page and Abercrombie, 1997;Thomas et al, 1998). Furthermore, fluoxetine exhibits moderate affinity for the norepinephrine transporter (NET) and very low affinity for the dopamine transporter (DAT) in humans (Owens et al, 2001).…”

The Effect of Early Poststressor Intervention with Sertraline on Behavioral Responses in an Animal Model of Post-Traumatic Stress Disorder

“…for 7 days. The dose is based on that used previously by Marona-Lewicka and Nichols (1997); Thomas et al (1998); Maj and Rogoz (1999) and Kim et al (2002). Control groups were given 0.9% saline solution in the same manner in order to control for the stressful effect of the i.p.…”