Daily Melatonin Injections Research Articles

Rat brain melanin at different ages and after various treatments

Melanin was measured by a spectrophotofluorometric method in the brains of albino rats from birth to 20 months of age. The concentration of brain melanin increased from Day 1 until adult levels were reached at 1 month. Between 1 and 20 months of age no significant differences were found in brain melanin. Daily injections of α-MSH, MIF-I, melatonin, or diluent did not consistently alter the concentration of brain melanin and a high (40%) protein diet did not appear to increase it. After concurrent injections of α-MSH and theophylline, an initial elevation of the level of melanin in the brain of newborn rats was found beginning at Day 8 but by age 1 month the values had returned to control levels. The results show that the largest changes in the concentrations of melanin in the brains of rats occur with age during the first month after birth.

Refractoriness to the antigonadotrophic effects of melatonin in male hamsters and its interruption by exposure of the animals to long daily photoperiods

Exposure of adult male Syrian hamsters to artificially shortened photoperiods in the laboratory was followed by gonadal involution. Return of these animals to long days (light:ddark cycles of 14:10) resulted in regrowth of the reproductive organs, following which the animals were refractory to the normally antigonadotrophic effects of daily melatonin injections given late in the afternoon. When hamsters were kept under naturally shortening photoperiods beginning on October 19, their reproductive organs involuted and remained infantile until the following spring when they again recrudesced to adult size. These animals too were refractory to the inhibitory effects of daily afternoon melatonin injections. The refractory period to melatonin was interrupted by exposure of the animals to long days for 22 weeks.

Interaction of daily injections and subcutaneous reservoirs of melatonin on the reproductive physiology of female Syrian hamsters.

This study investigated the ability of continuously available melatonin (from sc melatonin-beeswax pellets that were implanted bi-weekly) in overcoming the antigonadotrophic action of single daily melatonin (25 microgram) injections given late in the light period to female Syrian hamsters kept in light:dark cycles of 14:10. The melatonin-beeswax pellets contained either 1, 50, 500 microgram, 1 or 10 mg melatonin and 25 mg beeswax. Daily melatonin injections into hamsters implanted with beeswax only caused vaginal acyclicity in 60% of the animals within 6 weeks. After 10 weeks of treatment, uterine weights and pituitary levels of immunoreactive prolactin were still greatly depressed. Beeswax pellets containing either 500 microgram, 1 or 10 mg melatonin overcame the inhibitory effects of daily melatonin injections. Thus, the vaginal cycles and pituitary hormone levels of these animals were indistinguishable from those of untreated control animals. Beeswax pellets containing either 1 or 50 microgram melatonin were incapable of counteracting the antigonadotrophic effects of daily injections of melatonin. This is the first report that continuously available melatonin can negate the effects of daily injections of melatonin in female hamsters. When measured after 10 weeks, none of the treatment procedures significantly influenced circulating levels of luteinizing hormone or prolactin.

Synchronization of a circadian rhythm in pinealectomized European starlings by daily injections of melatonin

We have tested the hypothesis that the avian pineal hormone, melatonin, which is produced in and secreted from the pineal body in a circadian temporal pattern is a chemical mediator which drives overt circadian functions. Pinealectomized European starlings (Sturnus vulgaris) kept in continuous dim light, received intramuscular injections of melatonin at the same time each day for several weeks. Control birds received only sesame oil injections. In 21 out of 22 birds, melatonin treatment resulted in the synchronization of locomotor activity with the 24 h injection rhythm. In contrast, activity of only one out of 10 control birds became synchronized with the daily control injections. These results are consistent with the hypothesis that the endogenous circadian rhythm of melatonin concentration provides an internal synchronizing agent, acting directly on other circadian oscillators. Alternatively, it seems possible that the exogenous rhythm exerts its effect indirectly by modifying the sleep-wake cycle.

Subcutaneous melatonin implants inhibit reproductive atrophy in male hamsters induced by daily melatonin injections.

Daily afternoon (at 7 p.m.) injections of melatonin (25 microng in oil) into adult male hamsters for 50 days led to atrophy of the testes and accessory sex organs (seminal vesicles and coagulating glands) and in a significant depression in pituitary LH and prolactin content and concentration. These actions of melatonin were prevented if the animals had been pinealectomized before the daily melatonin injections were begun. Likewise, if hamsters received a weekly subcutaneous implant of melatonin in beeswax (1 mg melatonin in 24 mg beeswax) the daily melatonin injections failed to inhibit the growth of the reproductive organs and to depress pituitary LH and prolactin levels. Beeswax by itself had no such effect.

The effects of pineal indoles given late in the light period on reproductive organs and pituitary prolactin levels in male golden hamsters.

Intact and pinealectomized adult male hamsters kept in light:dark cycles of 14:10 (in hours) were given daily injections of either 25 microgram melatonin, 5-methoxytryptophol, N-acetylserotonin, or 6-hydroxymelatonin at 19.00 hours (13h after lights on). The injections were continued for 50 consecutive days. The daily melatonin injections significantly elevated body weights and depressed the growth of the testes and accessory sex organs and pituitary prolactin levels in intact hamsters. By comparison, in pinealectomized animals daily afternoon melatonin injections failed to alter body or testicular weights or pituitary prolactin levels. These findings indicate that for single injections of melatonin to be antigonadotrophic in the male hamster, the pineal must be intact. In intact animals, 5-methoxytryptophol and N-acetylserotonin slightly depressed the growth of the reproductive organs and pituitary prolactin levels, respectively. Again, these effects were negated by removal of the pineal gland. 6-Hydroxymelatonin was without influence on any of the parameters of reproduction that were measured.

Effect of Melatonin on the Reproductive Systems of Male and Female Syrian Hamsters: A Diurnal Rhythm in Sensitivity to Melatonin12

Hamsters were maintained on a long photoperiod (14L:10D) and were injected once daily with melatonin (10-25 mug) or sesame oil. Males which received melatonin during the afternoon (e.g., 6.5-13.75 h after lights-on) showed regressed testes and decreased levels of serum LH and FSH after several weeks of treatment. Injections of the oil vehicle or injections of melatonin given in the morning (3 h after lights-on) had no detectable effect on testicular size or on serum gonadotropins. Females which received melatonin during the afternoon became acyclic after several weeks of treatment and showed a diurnal pattern of LH secretion. The acyclic females required 4-6 weeks to resume estrous cyclicity following termination of the melatonin injections. The effects of melatonin on gonadal function and on serum gonadotropin concentrations in both sexes were similar to the previously observed effects of prolonged exposure to short photoperiods. These results indicate that chronic daily injections of melatonin can depress reproductive function in hamsters and that the effectiveness of the injections is dependent upon the time of day at which they are administered.

Melatonin Inhibition of Reproduction in the Male Hamster: Its Dependency on Time of Day of Administration and on an Intact and Sympathetically Innervated Pineal Gland

The daily s.c injection of 25 microgram melatonin (MEL) in oil into adult male hamsters at 7 p.m. (lights on 6 a.m. to 8 p.m.) for 50 days caused involution of the tests, coagulation of gland and seminal vesicles and depression in pituitary prolactin (Prl) levels. Similar injections of MEL given at 9 a.m. completely failed to cause regression of the sex organs or a depression in pituitary Prl levels. Injections of MEL in the p.m. were completely ineffective in inhibiting either the growth of the gonads and adnexa or the pituitary Prl levels if the animals had been pinealectomized. Likewise, superior cervical ganglionectomy, decentralization of the superior cervical ganglia and anterior hypothalamic deafferetation, procedures which interfere with the sympathetic nerve supply to the pineal gland, negated the ability of p.m. MEL injections to inhibit reproduction in male hamsters. The results indicate that daily MEL injections are capable of suppressing reproductive physiology in male hamsters, but only when the indole is injected late in the light period, in this case, 13 h after light on. The findings also illustrate that daily p.m. MEL injections can inhibit reproduction only in animals that have an intact and sympathetically innervated pineal gland.

Pineal gland: Evidence for an influence on ethanol preference in male syrian hamsters

1. 1. If adult male hamsters kept in light: dark cycles of 14: 10 are given a choice to drink water or 5% ethanol, they show a preference for the alcohol solution. Hamsters that are pinealectomized exhibit a reduced preference for ethanol. 2. 2. Blinded hamsters show an exaggerated ethanol preference which is also reduced by either pinealectomy or decentralization of the superior cervical ganglia. 3. 3. Daily melatonin injections of subcutaneously implanted melatonin-beeswax pellets do not influence ethanol preference in hamsters.

Effect of the Pineal Gland on Alcohol Consumption by Congenitally Blind Male Rats

Congenitally blind rats drank more of a 5% alcohol solution than water while congenitally blind pinealectomized rats drank more water than did the intact rats. Daily injections of melatonin did not...

The influences of illumination, melatonin and pinealectomy on testicular function in the rat.

The results of these experiments suggest that indirect parameters such as changes in weight of sex tissues and accessory sex gland fructose are not always consistent and may, therefore, not adequately represent pineal-gonadal interrelations. Evaluation of testicular function, by direct measurement of secretion of the hormone testosterone, illustrated the proposed inhibitory actions of darkness and melatonin one month after the subjection of animals to the various stimuli, at a time when changes in ventral prostate weight were present but not maximal. The secretion of testicular testosterone was, however, markedly depressed by extended darkness at 4 weeks when compared with that found for rats exposed to a light cycle of L:D 23:1 hr. The treatment of rats with melatonin, produced a more pronounced inhibitory action on prostatic growth and effects were still operative at 8 weeks. In accordance with its reported anti-LH action, daily injection of melatonin lead to inhibition of testosterone secretion in vivo when examined after 4 weeks. The anti-gonadal nature of the pineal gland was further illustrated when its removal caused, in addition to stimulation of prostate growth, the enhancement of testosterone secretion rates 4 weeks after surgery.

AN INHIBITORY EFFECT OF MELATONIN ON THE ESTROUS PHASE OF THE ESTROUS CYCLE OF THE RODENT.

Microgram doses of melatonin decrease the incidence of vaginal smears that demonstrate estrous phases in Sprague- Dawley rats and C3H/HeN mice. This property is not shared by the precursors of melatonin, serotonin and N-acetylserotonin, or its major metabolite, 6-hydroxymelatonin. The minimum effective dose of melatonin is decreased when daily melatonin injections are started prior to gonadal maturation. Pinealectomy is followed by an increase in the incidence of estrus; this increase is inhibited by melatonin treatment. (Endocrinology75: 238, 1964)