CYCLOSPORINE TREATMENT IN HYPERPROLACTINEMIC MALE-RATS .2. EFFECTS AT THE HYPOTHALAMIC LEVEL

The effects of cyclosporine (CyA) on different hypothalamic regions and the ability of prolactin to counteract these effects were investigated in adult male rats. Hyperprolactinemia was induced either by implantation of a pituitary under the kidney capsule or by subcutaneous administration of diethylstilbestrol (DES) capsules. Both pituitary grafting and DES treatment resulted in the expected marked increase in plasma prolactin levels as compared to their respective controls. Norepinephrine (NE) content in the median eminence was reduced 3 weeks after pituitary grafting; this effect was reversed by CyA treatment. Dopamine (DA) content was reduced both 1 and 3 weeks after the transplant operations, and was not further modified by CyA treatment. The ratio DOPAC/DA, which provides an index of DA turnover, was increased in the median eminence both at 1 and 3 weeks after the transplant operation compared to sham-operated rats; CyA reversed this increase at 1 week, but potentiated the stimulatory effect of hyperprolactinemia on DA turnover at 3 weeks. NE and DA content were reduced significantly in the median eminence of rats with DES implants (DES-In); however, after removal of the DES capsules (DES-Out), these differences were abolished. As expected, hyperprolactinemia observed in DES-treated rats was associated with an increase in DA turnover in the median eminence. CyA produced divergent effects on the median eminence DOPAC/DA ratio in the two groups of DES-treated animals: no modifications were observed in the DES-In group, but the stimulatory effect of DES exposure was potentiated by CyA in DES-Out rats. The levels of NE, DA and 5-hydroxytryptamine (5-HT) in the medial basal hypothalamus (MBH) were reduced significantly in DES-In animals; CyA treatment reversed changes in NE content, but did not modify the effects of DES on DA and 5-HT content in this group. However, in the control (empty capsule) group, CyA administration was followed by a reduction in NE and 5-HT levels and an increase in DA levels in the MBH compared to vehicle-treated controls. In the anterior hypothalamus, NE levels increased 3 weeks after pituitary grafting, while 5-HT levels increased at both 1 and 3 weeks after transplantation. In contrast, the levels of NE and 5-HT in the anterior hypothalamus of DES-In animals were reduced significantly, whereas, in DES-Out rats, these effects were not evident. CyA did not modify neurotransmitter levels in the anterior hypothalamus in either pituitary-grafted or DES-treated rats. It can be concluded that CyA may alter hypothalamic function, in some measure counteracting the regulatory influence of prolactin at this level.