Pindolol increases extracellular 5-HT while inhibiting serotonergic neuronal activity.
The effects of pindolol, a beta-adrenoceptor blocker/putative 5-hydroxytryptamine (5-HT)1A/1B antagonist, on both the single-unit activity of serotonergic neurons in the dorsal raphe nucleus (DRN) and extracellular 5-HT levels in the caudate nucleus, were examined in freely moving cats. Administration of (+)-pindolol (1 and 10 mg/kg, s.c.) decreased neuronal activity and increased 5-HT levels in a dose- and time-dependent manner. The subsequent administration of WAY-100635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cycloh exanecarboxamide] (0.2 mg/kg, s.c.), a selective 5-HT1A receptor antagonist, blocked pindolol-induced neuronal suppression and potentiated 5-HT output. These results indicate that pindolol may be acting at the level of the nerve terminal to increase 5-HT.
Fornal
C A
CA
Department of Psychology, Princeton University, NJ 08544-1010, USA. fornal@princeton.edu
Martín
F J
FJ
Mendlin
A
A
Metzler
C W
CW
Bjorvatn
B
B
Jacobs
B L
BL
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002415:Cats; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects*; D010869:Pindolol / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013997:Time Factors
D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D010869:Pindolol