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

Present address: Biometric Research Institute, Suite 300,1300 N 17th Street, Arlington, VA 22209, USA.

David J. Nutt

University of Bristol, Psychopharmacology Unit School of Medical Sciences, University Walk, Bristol BS8 1TD, UK

R. Bruce Holman

University of Bristol, Psychopharmacology Unit School of Medical Sciences, University Walk, Bristol BS8 1TD, UK

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 ₂-antagonist idazoxan suggests that chronic drug treatment has reduced the sensitivity of cortical pre-synaptic ₂-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.

Key Words: antidepressants • brain micro dialysis • noradrenaline • SSRIs • serotonin • sertraline

Journal of Psychopharmacology, Vol. 12, No. 4, 366-370 (1998)
DOI: 10.1177/026988119801200406


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