Control of dorsal raphé 5-HT function by multiple 5-HT(1) autoreceptors: parallel purposes or pointless plurality?
The serotonergic cells of the dorsal raphé nucleus innervate much of the forebrain and are thought to be involved in the mechanism of action of antidepressants. Dysfunction of these cells might be involved in the neural mechanisms underlying depression and suicide. The traffic in pathways emanating from the dorsal raphé nucleus is controlled by 5-HT(1) autoreceptors. Until recently it was thought that the autoreceptors in the dorsal raphé nucleus were solely of the 5-HT(1A) subtype. In this article, we discuss evidence that the situation is more complex and that multiple 5-HT(1) subtypes govern different aspects of 5-HT function in the dorsal raphé nucleus presenting new therapeutic opportunities.
Stamford
J A
JA
Neurotransmission Laboratory, Academic Dept of Anaesthesia and Intensive Care, The Royal London and St Bartholomew's School of Medicine and Dentistry, Alexandra Wing, Royal London Hospital, Whitechapel, E1 1BB, London, UK.
Davidson
C
C
McLaughlin
D P
DP
Hopwood
S E
SE
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D017660:Autoreceptors / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D019281:Dimerization; D006168:Guinea Pigs; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D020033:Protein Isoforms / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000502:physiology*; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D015290:Second Messenger Systems / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018687:Antidepressive Agents, Second-Generation; D017660:Autoreceptors; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D010069:Oxadiazoles; D010879:Piperazines; D020033:Protein Isoforms; D011725:Pyridines; D011743:Pyrimidines; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013134:Spiperone; D018170:Sumatriptan; C097067:CP 94253; C470302:HTR1B protein, human; C090701:GR 127935; C043077:ipsapirone; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide