Fumihiko Kobayashi

偽妊娠ラットのnocturnal prolactin surge 発現とcholinergic system の関係

To elucidate the role of the cholinergic system in controlling the nocturnal prolactin (PRL) surge in the early stage of rat pseudopregnancy, the effects of subcutaneous or intracerebroventricular (ICV) injections of various cholinergic agonists and antagonists on the pattern of the nocturnal PRL surge were investigated. Pseudopregnancy was induced by stimulating the uterine cervix with a vibrator between 0630 h and 0700 h on the morning of estrus (Day 0). Blood samples for PRL analysis by RIA were obtained every two hours from 2300 h on Day 2 to 0900 h on Day 3 through an indwelling venous cannula, which was implanted on Day 1 under pentobarbital-Na anesthesia, or by decapitation at 0300 h on Day 3. For ICV injection of the drug, rats were implanted with a stainless steel guide cannula 1.0 mm above the right lateral ventricle on diestrus 1 of the estrous cycle. They were given cervical stimulation on the initial estrous morning after the above operation. Control rats given saline solution showed a nocturnal PRL surge between 0100 h and 0700 h on Day 3 in the present study. Atropine sulfate (70 and 700 mg/kg) injected subcutaneously resulted in the complete inhibition of the nocturnal PRL surge whenever given at 2100 h on Day 2, 0000 h on Day 3 and 0300 h on Day 3, which corresponded to 4 hours and 1 hour before and 2 hours after the starting of the nocturnal PRL surge, respectively. ICV injection of atropine sulfate (250 micrograms/rat) also inhibited the occurrence of the nocturnal PRL surge when given at 0000 h on Day 3, though a slight and transient elevation of plasma PRL levels were seen. Subcutaneous injection of pilocarpine hydrochloride (5 and 50 mg/kg), a cholinergic agonist, did not affect the elevation of plasma PRL concentration observed at 0300 h on Day 3 when administered 3 hours before. The other agonist, arecoline hydrochloride, also did not affect the pattern of the nocturnal PRL surge when administered intravenously between 2315 h on Day 2 and 0515 h on Day 3. Subcutaneous injection of pimozide (1 mg/kg), a dopaminergic antagonist, just after the administration of atropine sulfate (700 mg/kg) given at 0000 h on Day 3 overcame the inhibitory effect of the later compound on the nocturnal PRL surge. However, the high levels of plasma PRL concentration still remained at 0700 h and 0900 h on Day 3 without any decrease as observed in the controls. These results suggest that the cholinergic system may be involved as a modulator in controlling physiological mechanism(s) of the nocturnal PRL surge in pseudopregnant rats.