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Serotonin 5‐HT 1A Autoreceptor Blockade Potentiates the Ability of the 5‐HT Reuptake Inhibitor Citalopram to Increase Nerve Terminal Output of 5‐HT In Vivo: A Microdialysis Study
Author(s) -
Hjorth Stephan
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03217.x
Subject(s) - autoreceptor , microdialysis , citalopram , reuptake , reuptake inhibitor , serotonin , chemistry , 5 ht receptor , pharmacology , endocrinology , medicine , extracellular , receptor , biology , biochemistry
The present study addressed the possibility that disinhibition of serotonin (5‐HT) autoreceptor‐mediated negative feedback might potentiate the elevation of nerve terminal 5‐HT output induced by selective 5‐HT reuptake blockade. To this end, rats were given citalopram and the 5‐HT autoreceptor‐blocking agents ( S )‐UH‐301 (5‐HT 1A ) and (−)‐penbutolol (5‐HT 1A/1B ), and the effect on extracellular 5‐HT in the ventral hippocampus was monitored by means of in vivo microdialysis. Citalopram (5 mg/kg, s.c.) approximately doubled the 5‐HT output, a response that was markedly augmented by ( S )‐UH‐301 (3 mg/kg, s.c.) and (−)‐penbutolol (8 mg/kg, s.c.) and by combined treatment with ( S )‐UH‐301 (3 mg/kg, s.c.) plus (−)‐penbutolol (1 μ M ; via the dialysis perfusion medium), but not by (−)‐penbutolol (1 μ M ) alone. These findings provide evidence that 5‐HT, in particular 5‐HT 1A , autoreceptor‐mediated negative feedback mechanisms are pivotal in determining the nerve terminal 5‐HT output level after 5‐HT reuptake inhibition. These findings have important implications for the interplay between different processes controlling 5‐HT transmission in vivo and might possibly offer a lead toward novel, therapeutically exploitable principles.