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 mu M) and sumatriptan (1 nM-1 mu M), 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.