Suppression of annual testicular development in Indian Palm Squirrel, Funambulus pennanti by 8 hr temporal relationship of serotonin and dopamine precursor drugs

Temporal phase relation of circadian neural oscillations alters RFamide-related peptide-3 and testicular function in the mouse.

Abstract: In order to study the effect of the temporal synergism of neural oscillations on reproductive regulation and the response of RFamide-related peptide-3 (RFRP-3; a mammalian ortholog of avian gonadotropin-inhibitory hormone), expression of immunoreactive RFRP-3 in the neurons of the dorsomedial nucleus of the hypothalamus was monitored in sexually immature and mature laboratory mice (study I). In study II, the effects of serotonin and dopamine precursors (5-hydroxytryptophan and L-dihydroxyphenylalanine; injected daily, 8 or 12 h apart, for 13 days in 3-week-old mice) on testicular activity and immunoreactive RFRP-3 neurons were studied until 24 days after treatment. Results indicate high levels of expression of immunoreactive RFRP-3 in the sexually immature and 8-hour mice (simulating gonadal suppression), while a low level was noted in mature and 12-hour mice (simulating gonadal stimulation). These findings not only suggest the modulation of gonadal development in mice (during the course of puberty attainment) by changing the temporal phase relation of serotonergic and dopaminergic oscillations (as in some seasonally breeding species), but also demonstrate an inverse correlation of RFRP-3 neurons and gonadal activity in both control and experimental conditions.

Temporal synergism of neurotransmitters (serotonin and dopamine) affects testicular development in mice.

Abstract: The temporal phase relation of circadian oscillations is reported to regulate reproduction in many seasonally breeding avian and mammalian species, but its role in the reproductive regulation of continuous breeders is not yet known. Hence in the present study, six experimental groups of 3-week-old male Parkes strain mice, Mus musculus, were injected with 5-hydroxytryptophan (5-HTP, serotonin precursor) and L-dihydroxyphenylalanine (L-DOPA, dopamine precursor) at intervals of 0, 4, 8, 12, 16 or 20 hr (5mg/100g body weight per day for 13 days). Control mice received two daily injections of normal saline. When observed 24 days post-treatment, 8-hr mice exhibited low body weight and suppression of gonadal activity (spermatogenesis, sperm count/motility/viability and plasma testosterone concentration), while body weight and degree of gonadal development were higher in the 12-hr mice as compared to the controls. It is concluded that normal somatic and gonadal growth of pre-puberal mice may be suppressed with an 8-hr phase relation of circadian serotonergic and dopaminergic oscillations. On the other hand, a 12-hr phase relation accelerated the rate of gonadal maturation, while other relations led to more or less similar gonadal development as in the control mice. This study suggests the importance of circadian organization as a function of specific temporal phase relations of neural oscillations in the maturation of gonads. Although the exact mechanism still needs to be investigated, this seems to be mediated via effects on the neuroendocrine axis.

Reproductive phase dependent circadian variation in hypothalamic concentration of serotonin, dopamine and peripheral thyroxine levels in Japanese Quail following 5-HTP and L-DOPA administration at specific time intervals

Abstract: Temporal phase relations of circadian hypothalamic neurotransmitters are reported to regulate seasonal reproduction in some avian species. Present experiments were designed to study circadian variation in the hypothalamic concentration of neurotransmitters (serotonin and dopamine) and the plasma thyroxine level in sexually active (long day) and inactive (short day) Japanese Quail. A significant circadian cycle was noted in the hypothalamic content of both serotonin and dopamine, but with different patterns. In breeding Quail, peak activity of serotonin and dopamine was noted at 10.00 A.M. and 10.00 P.M. respectively i.e. at the interval of 12 hours. However, during sexually quiescent condition, peaks of both neurotransmitters occurred at 2.00 P.M. i.e. having a 0-hour temporal relationship. During the breeding phase, the plasma thyroxine level showed a biphasic pattern with two circadian peaks at 10.00 A.M. and 10.00 P.M. whereas in the non-breeding condition a single peak was observed at 10.00 A...

Effects of simulated hypo- and hyper-reproductive conditions on the characteristics of circadian rhythm in hypothalamic concentration of serotonin and dopamine and in plasma levels of thyroxine, triiodothyronine, and testosterone in Japanese quail, Coturnix coturnix japonica.

Abstract: In this study, hypo‐ and hyper‐reproductive conditions, as measured by concentrations of plasma testosterone in male Japanese quail held on long days LD 16:8, were experimentally simulated with injections of 5‐hydroxytryptophan (5‐HTP) and L‐dihydroxyphenylalanine, (L‐DOPA) with 8 h and 12 h phase angle differences between them in intact and melatonin‐treated birds. The effects of these treatments were assessed on the characteristics of the circadian rhythm in the hypothalamic concentration of serotonin (5‐HT), dopamine (DA), and plasma levels of thyroxine (T4), triiodothyronine (T3), and testosterone (T). These rhythms were also studied in sham‐operated (SO), pinealectomized (Px), vehicle‐ (Veh), and melatonin (Mel)‐treated birds. On the basis of the circadian mesors of the testosterone rhythms, three distinct categories could be identified: category A (i.e., normal breeding concentrations of plasma testosterone), which includes control, sham‐operated, and vehicle‐treated groups; category A+ (i.e., conce...

Influence of temporal relationships between serotonergic and dopaminergic precursors on the regulation of gonadal development in birds.

Abstract: This article is focused on the effect of specific phase relation of serotonergic and dopaminergic oscillations on the gonadal responses of different avian species. These species include (i) summer breeding birds – Red headed bunting (exhibiting post-reproductive absolute photorefractoriness) and Indian Weaver bird (which lacks absolute photorefractoriness), (ii) autumn breeding – Spotted munia and Lal munia (photoperiodic responses of which are distinctly different from that of any long day birds described thus far) and (iii) domesticated Japanese quail (which under natural day length breeds in summer, exhibits relative photorefractoriness, but breeds continuously if maintained in long photoperiod). Previous experiments have shown that daily administration of serotonin precursor 5-hydroxytryptophan and dopamine precursor L-dihydroxyphenylalanine given 8 h apart during progressive phase of gonadal cycle can lead to a significant decrease in gonadal activity. However, if given at an interval of 12 h it leads to an increase in gonadal activity and the effect of other intervals (0-, 4-, 16- and 20-h) were not different from control. Similar effects were observed during regressive phase of the gonadal cycle of above species except in those which display absolute photorefractory phase in their breeding cycle. This shows that, gonad of such species not only develop post-reproductive photorefractoriness but also becomes insensitive to the stimulatory effects of 5-HTP and L-DOPA when given at the interval of 12 h. It is suggested that, temporal phase relation of circadian serotonergic and dopaminergic oscillations is the basis of seasonality in birds and may alter the activity of neuroendocrine-gonadal axis not only under natural day length but also under experimental/different photoperiodic conditions. These results are in agreement with the internal coincidence model of photoperiodic time measurement and indicate that birds can detect specific phase relationship between the two neural oscillations for their reproductive regulations and circadian organization is intricately involved in the regulation of seasonality.

The Pineal and Its Hormones in the Control of Reproduction in Mammals

Abstract: ONLY A LITTLE over a decade ago, any discussion of the function of the pineal gland included qualifying adjectives such as alleged, supposed, and putative. In the same vein, since it connoted a hormonal function, rather than referring to the pineal as a gland, the phrase pineal organ was usually employed to describe this portion of the epithalamus. However, this is no longer the case, at least in mammals. By the usual criteria in endocrinology, the pineal now fulfills all the qualifications of an organ of internal secretion. Several major discoveries revolutionized ideas concerning the function of the pineal gland. Certainly, as noted frequently in other reviews, the isolation and identification of N-acetyl-5-methoxytryptamine (melatonin), a pineal hormone, from bovine pineal tissue by Lerner et al. (1, 2) provided a strong impetus for subsequent investigations on this sometimes exasperating organ. At least as important as this discovery, however, were the observations that light and darkness govern both ...

dl‐5‐Hydroxytryptophan‐induced changes in central monoamine neurons after peripheral decarboxylase inhibition*

Abstract: The histochemical effects of 500 and 1000 mg/kg of dl-5-hydroxy-tryptophan (5-HTP), both alone and in combination with a peripheral decarboxylase inhibitor (seryl-trihydroxy benzyl hydrazine; Ro 4–4602) have been examined on central monoamine neurons of rats by the Falck-Hillarp fluorescence technique that demonstrates monoamines and their precursors. 5-HTP alone or together with Ro 4–4602 caused only weak intraneuronal accumulation of 5-HT in the central 5-HT neurons, in spite of an increased entry of 5-HTP into the brain after Ro 4–4602 treatment, as shown by an increase in the specific neuropil fluorescence and a reduction of 5-HT accumulation in the cells of the capillary walls. Ro 4–4602 markedly potentiated the effects of 5-HTP on the central dopamine neurons, many of which became clearly yellow fluorescent. The mechanism of dopamine depletion by 5-HTP is probably therefore mainly one of displacement. The effects on the noradrenaline neurons were also potentiated by Ro 4–4602 pretreatment, the neurons exhibiting a yellow-green fluorescence. This depletion may therefore also be mainly be due to amine displacement. It is concluded that the ability of the 5-HT neurons to take up and accumulate 5-HT in the presence of 5-HTP is relatively low in spite of large amounts of 5-HTP present in the brain neuropil after extracerebral decarboxylase inhibition.

In vivo release of 5-HT in the lateral ventricle of the rat: effects of 5-hydroxytryptophan and tryptophan.

Abstract: The in vivo release of 5-HT was examined in the rat brain. For this purpose, the left lateral ventricle was perfused at a constant rate with an artificial CSF for several hours in animals anaesthetized with halothane. 5-HT was estimated in serial 1-h collected fractions. The amine was first isolated by adsorption on a Sephadex G-10 column and then assayed using the radioenzymatic method of Saavedra et al.37, slightly modified to improve its sensitivity. The quantity of 5-HT released spontaneously during the first hour fraction was 296 pg, it was lower (99 pg/h) in the following fractions. 5-HT released into the CSF may in great part originate from serotoninergic terminals localized in structures surrounding the ventricle. This was suggested by experiments in which exogenous [3H]5-HT or [3H]tryptophan were perfused through the lateral ventricle during a few hours. [3H]5-HT taken up or synthetized was mainly localized in structures surrounding the ventricular space. The acute injection of 5-hydroxytryptophan (100 mg/kg) induced an immediate important and long lasting increase of 5-HT release. In contrast the acute injection of tryptophan (100 mg/kg) led to a transient and moderate elevation of 5-HT release which was only detected during the second hour of perfusion. Curiously a similar pattern of transmitter release was observed following the constant intravenous infusion of the amino acid (70 mg/kg/h) except that the increase in 5-HT release was much more pronounced during the second hour than after the acute injection. Parallel experiments were made to determine the time course of the changes of free and total tryptophan levels in plasma and of those of tryptophan, 5-HT, and 5-hydroxyindoleacetic-acid (5-HIAA) in brain tissues, induced by the acute and long term administrations of tryptophan. Moreover the rate of 5-HT synthesis was estimated using the monoamine oxidase inhibition method 2 and 5 h after both tryptophan treatments in halothane anaesthetized rats. 5-HT levels and the synthesis rate of the transmitter were increased at 2 h (when both tryptophan treatments stimulated 5-HT release). Despite the presence of high tryptophan levels in plasma and tissues and of high 5-HT and 5-HIAA levels in tissues, the synthesis rate of 5-HT (as the 5-HT release) was similar to that of controls 5 h after the onset of tryptophan infusion. These results suggest that some relationships occurred between the changes in 5-HT SYNTHESIs and release after the first hour of perfusion. The absence of effects of tryptophan treatments on 5-HT release during the first hour of perfusion are also discussed.