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In several species, including man and the rat, hyperprolactinaemia is associated with suppression of gonadotrophin release and male sexual behaviour. However, in the hyperprolactinaemic male mouse, plasma LH and FSH levels and copulatory behaviour are increased rather than suppressed. In an attempt to identify mechanism(s) which may be responsible for these effects of hyperprolactinaemia in the mouse, we have examined the effects of two ectopic pituitary isografts on several indices of hypothalamic and pituitary function in adult DBA/2J males. Animals with pituitary grafts had markedly increased plasma concentrations of prolactin, LH and FSH and enlarged seminal vesicles, whereas testicular and pituitary weights were not affected. Content of LHRH receptors and activity of aromatase in the pituitary, as well as dopamine-β-hydroxylase activity in the hypothalamus were nearly identical in pituitary-grafted and sham-operated males. Biosynthesis of dopamine and turnover of noradrenaline in the median eminence were significantly increased in grafted males. We suggest that the increase in the activity of hypothalamic noradrenergic neurones may mediate stimulatory action of hyperprolactinaemia on LH and FSH release in the mouse. Comparison of these results with those obtained previously in the rat suggests that species differences in the effects of prolactin on gonadotrophin release may be related to its divergent effects on noradrenaline turnover.J. Endocr.(1987) 112,215–220

Summary.Injection of the dopamine hydroxylase inhibitor U-14,624, to ovariectomized rats resulted in the reduction of hypothalamic norepinephrine concentration over a 48-h period and the elevation of hypothalamic dopamine concentration over a 24-h period. Plasma LH and FSH levels were markedly suppressed up to 48 h after drug treatment. These results suggest that U-14,624 is a much more potent inhibitor of gonadotrophin secretion than has been previously reported.

Female Sprague-Dawley rats were placed on a 6-week barbital feeding regimen, previously documented to result in drug tolerance and dependence. Groups of animals were sacrificed on the 2nd and 5th day of each week, up to week 5, or at various time points following drug withdrawal. Cerebellae and cerebral cortices were collected for cyclic GMP (cGMP) measurements. Initial suppressions of cGMP were seen in both the cerebellum and cerebral cortex during early weeks of the feeding regimen. These gradually returned essentially to control levels by the end of 5 weeks, a finding consistent with the development of tolerance to chronic barbiturates in the cGMP system. Barbital was withdrawn after 6 weeks of chronic administration. Four hours after withdrawal, a dramatic elevation of cerebellar cGMP was seen. This elevation was coincident with a significant decline in serum barbital levels and preceded the onset of weight loss, spontaneous seizures and locomotor depression. The elevation of cGMP was less dramatic but still apparent at 72 hr postwithdrawal when all other evaluated parameters had returned to control values. Alterations of cGMP during chronic barbital treatment and subsequent to abrupt barbital withdrawal may reflect aberrations in the function of neurotransmitter pathways involved in regulating cGMP in the cerebellum. Further, the elevation of cGMP after barbiturate withdrawal may itself play a functional role in the manifestation of barbital abstinence.

The effects of inhibiting gamma-aminobutyric acid-transaminase (GABA-T) with aminooxyacetic acid or with gabaculine and inhibiting GABA uptake with nipecotic acid on dopamine (DA) synthesis in the retina of light-exposed rats were studied. 3,4-Dihydroxyphenylalanine (Dopa) accumulation after the inhibition of L-aromatic amino acid decarboxylase with NSD-1015 was used as an index of DA synthesis. The GABA-T inhibitors significantly increased GABA levels in the retina but had no effect on retinal Dopa accumulation in the light. Dopa accumulation was significantly inhibited at a high dosage by nipecotic acid alone and by low dosages of nipecotic acid in rats pretreated with either aminooxyacetic acid or gabaculine. The dosages of nipecotic acid which inhibited Dopa accumulation in the light also inhibited [3H]GABA uptake in the retina. The inhibitory effects of gabaculine and nipecotic acid on Dopa accumulation appeared to occur at least partially via GABA receptors because their action was significantly reversed by the GABA antagonist bicuculline methiodide. These experiments thus suggest that endogenous GABA can suppress the light-evoked increase in DA synthesis in the rat retina and support previous studies which concluded that an inhibitory GABA input may at least partially regulate the activity of the DA neurons in the retina of rats.