Somatodendritic action of pindolol to attenuate the paroxetine-induced decrease in serotonin release from the rat ventral hippocampus: a microdialysis study.
We used intracerebral microdialysis to study the role of raphe and presynaptic serotonin (5-HT) autoreceptors in the effect of the selective 5-HT reuptake inhibitor, paroxetine, on 5-HT release from ventral hippocampus of anaesthetised rats. In addition, we have tested the ability of pindolol, a non-selective beta-adrenergic/5-HT(1A) receptor antagonist, to alter the response of hippocampal 5-HT to paroxetine. Doses of paroxetine with maximal effects were near to three-fold less effective when administered systemically than after local infusion at increasing extracellular 5-HT in ventral hippocampus. Moreover, systemic paroxetine treatment resulted in a marked decrease of the extracellular 5-HT in the hippocampus when 5-HT reuptake was blocked with paroxetine 3 microM applied locally, thereby evidencing that systemic treatment induced a decrease of 5-HT release in the neuronal terminal. A similar drop was observed when paroxetine 3 microM was perfused into the median raphe, a region that contains the cell bodies of the neurons innervating the ventral hippocampus. Racemic (+/-)-pindolol (10 mg/kg, s.c.) completely blocked the paroxetine-induced decrease in 5-HT release from rat hippocampus. In addition, the infusion into median raphe of (-)-pindolol, the isoform with highest antagonist activity, at concentrations of 10 microM and 100 microM was able to partially block the decrease of hippocampal 5-HT release after systemic paroxetine. However, perfusion of (-)-pindolol into the hippocampus was without effect on local 5-HT release. These data suggest that pindolol acts preferentially through the blockade of somatodendritic 5-HT(1A) autoreceptors to restore the decline in 5-HT outflow in rat forebrain following systemic administration of selective 5-HT reuptake inhibitors.
Míguez
Jesús M
JM
Laboratory Fisioloxía Animal, Departamento Bioloxía Funcional e Ciencias da Saude, Facultade de Ciencias, Universidade de Vigo, 36200 Vigo, Spain. jmmiguez@uvigo.es
Paz-Valiñas
Lucinda
L
Míguez
Isabel
I
Aldegunde
Manuel
M
D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000502:physiology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017374:Paroxetine / Q000494:pharmacology; D010869:Pindolol / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000737:chemistry / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013237:Stereoisomerism; D009435:Synaptic Transmission / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D017660:Autoreceptors; D006897:Hydroxyindoleacetic Acid; D017374:Paroxetine; D010869:Pindolol; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors