Pindolol increases extracellular 5-HT while inhibiting serotonergic neuronal activity

The effects of pindolol, a beta-adrenoceptor blocker/putative 5-hydroxytryp tamine (5-HT)(1A/1B) antagonist, on both the single-unit activity of seroto nergic neurons in the dorsal raphe nucleus (DRN) and extracellular 5-HT lev els in the caudate nucleus, were examined in freely moving cats. Administra tion of (+/-)-pindolol (1 and 10 mg/kg, s.c.) decreased neuronal activity a nd increased 5-HT levels in a dose- and time-dependent manner. The subseque nt administration of WAY-100635 {N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]et hyl]-N-(2-pyridinyl)cyclohexanecarboxamide} (0.2 mg/kg, s.c.), a selective 5-HT1A receptor antagonist, blocked pindolol-induced neuronal suppression a nd potentiated 5-HT output. These results indicate that pindolol may be act ing at the level of the nerve terminal to increase 5-HT. (C) 1999 Elsevier Science B.V. All rights reserved.