Chronic paroxetine desensitises 5-HT1D but not 5-HT1B autoreceptors in rat lateral geniculate nucleus.
The present study examined the effect of chronic paroxetine (10 mg/kg p.o., 21 days) on the 5-HT1B and 5-HT1D autoreceptors controlling 5-HT efflux in slices of rat ventrolateral geniculate nucleus. Electrically stimulated 5-HT efflux (10 pulses, 200 Hz, 0.1 ms, 10 mA) was measured using fast cyclic voltammetry. Peak 5-HT efflux was greater (P < 0.01) after chronic paroxetine (22.2 +/- 1.4 nM, mean +/- S.E.M.) than water (15.8 +/- 1.4 nM). 5-HT efflux was inhibited by CP 93129 (1 nM-10 microM) and sumatriptan (1 nM-1 microM), agonists at 5-HT1B and 5-HT1D receptors, respectively. Chronic paroxetine did not affect the sensitivity of the 5-HT1B autoreceptor but shifted the sumatriptan concentration-response curve to the right (P < 0.05). These data suggest that chronic paroxetine increases evoked 5-HT efflux. This may be the result of desensitisation of 5-HT1D but not 5-HT1B autoreceptors.
Davidson
C
C
Anaesthetics Unit (Neurotransmission Laboratory), St. Bartholomew's and the Royal London School of Medicine and Dentistry, Royal London Hospital, Whitechapel, UK.
Stamford
J A
JA
D000818:Animals; D017660:Autoreceptors / Q000187:drug effects*; D005829:Geniculate Bodies / Q000187:drug effects*; D008297:Male; D017374:Paroxetine / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology; D013997:Time Factors
D017660:Autoreceptors; D017374:Paroxetine; D011725:Pyridines; D011758:Pyrroles; D011985:Receptors, Serotonin; 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