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  • Title: Further evidence for the importance of 5-HT1A autoreceptors in the action of selective serotonin reuptake inhibitors.
    Author: Hjorth S, Auerbach SB.
    Journal: Eur J Pharmacol; 1994 Aug 01; 260(2-3):251-5. PubMed ID: 7988652.
    Abstract:
    The clinical efficacy of antidepressants that block serotonin (5-hydroxytryptamine, 5-HT) reuptake may be restrained by indirect activation of autoreceptors. In vivo microdialysis in rat hippocampus was used to assess the release-inhibitory properties of the 5-HT reuptake inhibitors citalopram and paroxetine. When reuptake was first blocked by infusing citalopram into the hippocampus, systemic administration of citalopram or paroxetine resulted in a 50-70% decrease in hippocampal 5-HT overflow. This presumably reflected the inhibition of 5-HT release subsequent to reuptake blockade in the raphe nuclei and, in turn, activation of somatodendritic autoreceptors. In support, pretreatment with (+/-)-pindolol or (+)-WAY100135 ((+)-N-tert-butyl-3-(4-(2- methoxyphenyl)piperazine-1-yl)-2-phenylpropanamide dihydrochloride), to block 5-HT1A autoreceptors, abolished the decrease in 5-HT produced by systemic injection of the uptake blockers.
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