Modulation of the firing activity of rat serotonin and noradrenaline neurons by (±)pindolol

Background: (±)Pindolol is a β-adrenergic/5-HT1A receptor antagonist used in combination with certain antidepressant drugs to accelerate the onset of the antidepressive response. Methods: The aim of the present study was to assess, using an in vivo electrophysiologic paradigm, the effect of (±)pindolol on the spontaneous firing activity of rat dorsal raphe serotonin (5-HT) and locus coeruleus noradrenaline (NA) neurons. Results: (±)Pindolol did not modify the firing activity of dorsal raphe 5-HT neurons at low doses (10 and 200 μg/kg, IV), but it prevented the suppressant effect of the 5-HT autoreceptor agonist lysergic acid diethylamide (LSD, 10 μg/kg, IV) but not that of the 5-HT1A receptor 8-hydroxy-N,N-dipropyl-aminotetralin (8-OHDPAT, 5 μg/kg, IV). At a higher dose (500 μg/kg, IV), (±)pindolol decreased 5-HT neuronal firing and this effect was reversed by the selective 5-HT1A receptor antagonist WAY 100635 (100 μg/kg, IV), suggesting that it could act as a partial 5-HT1A autoreceptor agonist. In the locus coeruleus, the high dose of (±)pindolol decreased the firing activity of NA neurons and this effect was reversed by the 5-HT2A receptor antagonist MDL 100907 (200 μg/kg, IV). Finally, both a lesion of NA neurons and the administration of MDL 100907 prevented the suppressant effect of (±)pindolol on the firing of 5-HT neurons. Conclusions: It is suggested that, at low doses, (±)pindolol acts as a somatodendritic 5-HT1A autoreceptor antagonist whereas at a higher dose, it decreases the tonic excitatory input from NA neurons to 5-HT neurons