Effects of 5-hydroxytryptamine uptake blockers on the release of LH and prolactin in several different experimental steroid models in the rat

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Abstract
The effect of the 5-hydroxytryptamine (5-HT) uptake blockers on the surges of LH and prolactin has been investigated in pro-oestrous rats and various experimental models used frequently to study the effects of steroids on LH and prolactin secretion in female rats. The steroid models were: rats ovariectomized on dioestrus, injected immediately with oestradiol benzoate (OB) and at 12.00 h on the next day (presumptive pro-oestrus) with progesterone (model 1); long-term ovariectomized rats injected with a single injection of OB and 72 h later with either progesterone (model 2) or OB (model 3); long-term ovariectomized rats injected daily with OB (model 4). The uptake blockers alaproclate (3–30 mg/kg) and zimelidine (20 mg/kg) were injected and blood samples withdrawn from previously implanted intra-atrial cannulae. Plasma LH and prolactin concentrations were determined by radioimmunoassay. The present study confirmed that a surge of LH occurs at about 17.00–18.00 h of the presumptive day of pro-oestrus in model 1, at about 5 h after (∼ 17.00 h) the injection of either progesterone or the second injection of OB in models 2 and 3, and diurnally in model 4, and the simultaneous occurrence of a prolactin surge in models 2 and 4. A surge of prolactin at the same time as the LH surge was shown to occur also in models 1 and 3. Alaproclate (30 mg/kg) administered at 15.00 h delayed significantly the peak of the prolactin surge in the pro-oestrous rat and models 1, 3 and 4, and in the latter the magnitude of the prolactin surge was also significantly reduced. By contrast, the peak of the prolactin surge in model 2 was significantly prolonged by alaproclate. Alaproclate had no significant effect on either the timing or the magnitude of the LH surge in the pro-oestrous rat, and models 3 and 4. The peak of the LH surge was delayed by alaproclate in model 1 and abolished in model 2, providing further evidence for the possible importance of interactions between 5-HT and progesterone in neuroendocrine control. Zimelidine had no significant effect on either the LH or prolactin surge in the pro-oestrous rat and in models 1 and 2. These results show that normal 5-HT uptake is necessary for the normal timing and/or magnitude of the spontaneous and steroid-induced prolactin surge but is not essential for the normal timing and magnitude of the spontaneous surge of LH and the LH surge in some but not all steroid models. In terms of neuroendocrine effects alaproclate is more potent than zimelidine. The different effects of alaproclate in the different steroid models suggest that although superficially similar, different mechanisms underlie the prolactin and LH surges in these steroid models. J. Endocr. (1985) 104, 397–406

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