A Chronically Hypoprolactinemic Rat Model: Administration of Lergotrile Mesylate by Osmotic Minipump

Abstract

The feasibility of developing a hypoprolactinemic animal model by inducing prolonged suppression of endogenous prolactin (PRL) secretion by lergotrile mesylate (LM) administered via an ip implanted osmotic minipump was investigated. The response of plasma PRL to a 3-min ether challenge was examined over 7 days in animals receiving either physiological saline or LM at rates of 2.5, 5.0, and 10.0 μg/hr via osmotic minipumps. Control animals demonstrated an increased PRL response to ether, in comparison to Day 1, upon subsequent exposures. The increased response to subsequent ether exposure was prevented by LM administration at rates of 2.5 and 5.0 μg/hr. LM at a rate of 10.0 μg/hr significantly suppressed the PRL response to ether on Days 4, 6 (P < 0.001), and 7 (P > 0.002) following pump implantation. In addition, spontaneous PRL levels were examined over a 24-hr period in chronically cannulated male rats receiving either saline (n = 4) or LM at a rate of 10.0 μg/hr (n = 4), on Day 7 following pump implantation. LM administration prevented the diurnal surge which appeared in saline-treated animals from 1400 to 1600 hr (P < 0.001), and lowered the mean 24-hr plasma PRL concentration from 19.7 ± 1.7 ng/ml in controls to 13.2 ± 0.4 ng/ml (P < 0.005). These data indicate that constant LM administration by osmotic minipump at a rate of 10.0 μg/hr (0.69 mg/kg/day) is sufficient to suppress both spontaneous and ether-stimulated PRL secretion in adult male rats. This route of LM administration is preferable to ip injection for suppression of PRL secretion over a prolonged period of time, as it reduces the amount of drug required for suppression, possibly decreasing side effects, and also reduces the amount of handling of animals during the course of an experiment.