Effect of chronic paroxetine treatment on 5-HT1B and 5-HT1D autoreceptors in rat dorsal raphe nucleus.
This study reports the effect of chronic paroxetine (10 mg/kg p.o., 21 days) on 5-HT1B and 5-HT1D autoreceptors controlling stimulated 5-HT efflux in slices of rat dorsal raphe nucleus. Electrically evoked 5-HT (10 pulses, 200 Hz, 0.1 ms, 10 mA) was measured using fast cyclic voltammetry. 5-HT efflux was inhibited by CP 93129 (10 nM-10 microM) and by sumatriptan (1 nM-1 microM) agonists at 5-HT1B and 5-HT1D receptors, respectively. Chronic paroxetine did not, initially, appear to alter the sensitivity of the 5-HT1B autoreceptors to CP 93129. However, when constructed in the presence of WAY 100635 (10 nM) the selective and silent 5-HT1A antagonist, there was a significant (P < 0.001) rightward shift of the CP 93129 concentration-response curve in the paroxetine-treated rats but not in the controls, implying a desensitisation of the 5-HT1B autoreceptor by paroxetine. Chronic paroxetine did not affect the sumatriptan concentration-response curve, even with WAY 100635 present, implying that there was no (de)sensitisation of the 5-HT1D autoreceptor. These data suggest that chronic paroxetine treatment may desensitise 5-HT1B autoreceptors in the dorsal raphe nucleus but that this effect is unmasked only when the dominant 5-HT1A autoreceptor control is antagonised.
Davidson
C
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Academic Department of Anaesthesia and Intensive Care, St Bartholomew's and the Royal London School of Medicine and Dentistry, Royal London Hospital, Whitechapel, London, UK.
Stamford
J A
JA
D000818:Animals; D004558:Electric Stimulation; D008297:Male; D017374:Paroxetine / Q000008:administration & dosage / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011903:Raphe Nuclei / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology
D017374:Paroxetine; D010879:Piperazines; D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D018170:Sumatriptan; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide