Interaction between a selective 5‐HT1Areceptor antagonist and an SSRI in vivo: effects on 5‐HT cell firing and extracellular 5‐HT

• DOI: 10.1111/j.1476-5381.1995.tb15919.x
• Publication Date: 2012-07-19T21:45:03Z
• Authors: S.E. Gartside; V. Umbers; M. Hajós; T. Sharp
• Keywords: Paroxetine; Microdialysis; Dorsal raphe nucleus; Raphe nuclei

The acute inhibitory effect of selective 5‐hydroxytryptamine (serotonin) reuptake inhibitors (SSRIs) on 5‐HT neuronal activity may offset their ability to increase synaptic in the forebrain. 2Here, we determined effects SSRI, paroxetine, and a novel 1A receptor antagonist, WAY 100635, cell firing dorsal raphe nucleus (DRN), extracellular both DRN frontal cortex (FCx). Extracellular electrophysiological recording brain microdialysis were used parallel experiments, anaesthetized rats. Paroxetine dose‐dependently inhibited neurones DRN, with maximally effective dose approximately 0.8 mg kg −1 , i.v. 100635 (0.1 i.v.) reversed paroxetine and, when as pretreatment, caused pronounced shift right dose‐response curve. (0.8 i.v.), doubled but did not alter FCx. A higher (2.4 FCx, lesser extent than DRN. Whereas alone had no rats pretreated ), markedly increased In conclusion, pretreatment blocked at same time, enhanced These results be relevant recent clinical observations that antagonists combination SSRIs have rapid onset antidepressant effect.