text: Modulation of dialysate levels of dopamine, noradrenaline, and serotonin (5-HT) in the frontal cortex of freely-moving rats by (-)-pindolol alone and in association with 5-HT reuptake inhibitors: comparative roles of beta-adrenergic, 5-HT1A, and 5-HT1B receptors.
  (-)-Pindolol, which possesses significant affinity for 5-HT1A, 5-HT1B, and beta 1/2-adrenergic receptors (AR)s, dose-dependently increased extracellular levels of dopamine (DA) and noradrenaline (NAD) versus 5-HT, in dialysates of the frontal cortex (FCX), but not accumbens and striatum, of freely-moving rats. In distinction, the preferential beta 1-AR antagonist, betaxolol, and the preferential beta 2-AR antagonist, ICI118,551, did not increase basal levels of DA, NAD, or 5-HT. Further, they both dose-dependently and markedly blunted the influence of (-)-pindolol upon DA and NAD levels. The selective 5-HT1A receptor antagonist, WAY100,635, slightly attenuated the (-)-pindolol-induced increase in DA and NAD levels, while the selective 5-HT1B antagonist, SB224,289, was ineffective. These data suggest that (-)-pindolol facilitates frontocortical dopaminergic (and adrenergic) transmission primarily by activation of beta 1/2-ARs and, to a lesser degree, by stimulation of 5-HT1A receptors, whereas 5-HT1B receptors are not involved. (-)-Pindolol potentiated the increase in FCX levels of 5-HT elicited by the 5-HT reuptake inhibitors, fluoxetine and duloxetine, and also enhanced their ability to elevate FCX levels of DA--though not of NAD. In contrast to (-)-pindolol, betaxolol and ICI118,551 did not affect the actions of fluoxetine, whereas both WAY100,635 and SB224,289 potentiated the increase in levels of 5-HT--but not DA or NAD levels--elicited by fluoxetine. In conclusion, (-)-pindolol modulates, both alone and together with 5-HT reuptake inhibitors, dopaminergic, adrenergic, and serotonergic transmission in the FCX via a complex pattern of actions at beta 1/2-ARs, 5-HT1A, and 5-HT1B receptors. These findings have important implications for clinical studies of the influence of (-)-pindolol upon the actions of antidepressant agents.
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entities.type: CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-N GENE-N CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-N CHEMICAL GENE-Y GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL
entities.text: betaxolol ICI118,551 fluoxetine WAY100,635 SB224,289 5-HT DA NAD fluoxetine (-)-pindolol (-)-Pindolol 5-HT dopamine DA (-)-pindolol noradrenaline NAD 5-HT betaxolol ICI118,551 DA (-)-Pindolol NAD 5-HT (-)-pindolol DA NAD WAY100,635 (-)-pindolol DA NAD SB224,289 5-HT (-)-pindolol (-)-pindolol 5-HT dopamine noradrenaline serotonin 5-HT 5-HT1B (AR)s beta 1/2-ARs 5-HT 5-HT1A 5-HT1B beta 1-AR beta 2-AR 5-HT1A 5-HT1A 5-HT1B 5-HT1B beta 1/2-adrenergic receptors beta 1/2-ARs fluoxetine 5-HT1A 5-HT1A, 5-HT1B duloxetine DA NAD (-)-pindolol