Partial 5-HT1A receptor agonist properties of (-)pindolol in combination with citalopram on serotonergic dorsal raphe cell firing in vivo

Rationale: Pindolol has been reported to shorten the onset of antidepressan t action of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibi tors (SSRIs) as well as to increase their efficacy. It has been postulated that pindolol enhances the antidepressant effect of SSRIs by blocking somat odendritic 5-HT1A autoreceptors, thus antagonizing the SSRI-induced feedbac k inhibition of midbrain 5-HT cell firing. A recent study, however, found t hat pindolol suppresses the firing rate of central 5-HT cells, suggesting t hat the compound possesses agonistic activity at 5-HT1A autoreceptors. Obje ctives: The pul pose of the present study was to investigate if acute admin istration of (-)pindolol antagonizes the decrease in firing rate of dorsal raphe 5-HT cells produced by acute treatment with the SSRI citalopram. Meth ods: Extracellular recordings of single 5-HT neurons in the dorsal raphe nu cleus in anaesthetized rats. Results: Administration of 0.25 or 3.0 mg/kg ( IV) (-)pindolol alone decreased the firing rate of a majority of the 5-HT c ells studied, an effect that was reversed by the 5-HT1A receptor antagonist WAY100635 (0.1 mg/kg, IV). Neither 0.25 nor 3.0 mg/kg (-)pindolol reversed the citalopram (0.1-0.2 mg/kg, IV)-induced suppression of 5-HT cell activi ty, but produced a further decrease in firing rate. In contrast, WAY100635 (0.1 mg/kg) completely reversed this effect of citalopram. Yet, pretreatmen t with 3.0, but not 0.25 mg/kg (-)pindolol significantly attenuated the acu te inhibitory effect of citalopram on serotonergic cell firing. Conclusions : The present findings support the previous notion that (-)pindolol possess es prominent agonistic activity at somatodendritic 5-HT1A autoreceptors, bu t also indicate that it may possess a weak antagonistic action at these rec eptors.