Further evidence for the importance of 5-HT1A autoreceptors in the action of selective serotonin reuptake inhibitors.
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.
Hjorth
S
S
Department of Pharmacology, University of Göteborg, Sweden.
Auerbach
S B
SB
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D017660:Autoreceptors / Q000187:drug effects* / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017374:Paroxetine / Q000494:pharmacology; D010869:Pindolol / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013237:Stereoisomerism
D000928:Antidepressive Agents; D017660:Autoreceptors; D015283:Citalopram; D017374:Paroxetine; D010869:Pindolol; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C081293:WAY 100135