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1. 1. Mice of four ages between newborn and adult were exposed to the monoamine oxidase inhibitor amiflamine both acutely and in an extended (5 day) regimen. Brains were then assayed at various times following amiflamine for changes in the levels of serotonin (5-HT, 5-hydroxytryptamine) and 5-hydroxyindole acetic acid (5-HIAA). 2. 2. Although both metabolites initially changed as might be expected, with 5-HT elevating and 5-HIAA decreasing, the younger brains recovered their 5-HT levels slower than older brains and eventually young brains had levels of 5-HIAA that were in excess of normal. At some times both metabolites were in excess of normal at younger ages. 3. 3. These results are compared to changes seen with the 5-HT uptake inhibitor citalopram and it is concluded that in young brain 5-HIAA levels lack firm regulatory control and are not passive reflections of 5-HT changes.

1. 1. Mice at various ages between birth and adulthood were injected with cocaine hydrochloride (30 mg/kg) and then their brains were assayed for 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA). 2. 2. Changes in the levels of both metabolites were in keeping with 5-HT uptake inhibition at all ages.

1. Mice of various ages between birth and adulthood were injected daily for 12 days with the serotonin specific uptake inhibitor citalopram (LU 10-171). 2. Two hours, 1 day and 3 days following the last injection animals were killed and their brains assayed for 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA). 3. Changes in levels of both metabolites varied by age of the animal, brain region and time after last injection. These patterns differed from previous studies of shorter duration citalopram exposure. 4. The data support the view that 5-HT and 5-HIAA levels are probably not dependently related in immature brain. Indeed 5-HIAA modulation in the immature seems to lack the firm control of the adult and can be modified for extended periods by citalopram action.

Mice between the ages of 1 day postpartum and adulthood were exposed to the monoamine oxidase inhibitors tranylcypromine and pargyline. The mice were killed at seven different times following drug injection and assayed in vitro for monoamine oxidase activity in four brain regions. Inhibition and recovery of monoamine oxidase activity varied by age, and with the two inhibitors used. During the early maturational period, the potential for new monoamine oxidase synthesis was greater than normal maturational patterns of increase would suggest; and during later maturation either the proportions of various monoamine oxidase forms or their rates of synthesis are different.

Monoamine oxidase (MAO) was assayed in mouse brain between the ages of 1 day postpartum and adulthood. Two substrates, 5-hydroxytryptamine (5-HT) and tryptamine, were used and assays were done with and without thermal inactivation at 50 °C for 10 min. Relative patterns of MAO maturation were found including one form that decreased with increasing age.

Trytophan-5-hydroxylase (T5-H) has been measured in four subdivisions of the mouse brain during various stages of postnatal maturation. Patterns of T5-H maturation are very similar to previously measured 5-hydroxytryptamine patterns of maturation. Regional variation is evidenced and most pronounced in the period following the first week after birth. The similarity of maturational pattern for tryptophan-5-hydroxylase and 5-hydroxytryptamine lends support to the idea that the enzyme is a controling factor in the brain’s indoleamine maturation; however, there are reasons to believe that such a conclusion is premature.

Mating pairs of mice were maintained continuously on drinking water containing 50 mEq/l LiCl and its effects on reproduction and postnatal development were monitored. In mating pairs put on lithium at 6–8 weeks of age, the lithium does not appear to reduce litter size at birth but it does increase postnatal mortality and the length of time between litters, and reduces the total number of litters a mating pair may have. In mating pairs put on lithium at 3 weeks of age, it severely delays postnatal growth and development of all pups in the litter. With the exception of the liver, this delayed growth and development does not appear to affect internal organs as severely as somatic body parts. This delayed growth may be the result of some effect lithium may have on certain hormones such as prolactin, thyroxine and growth hormone.

The maturation of various enzymes and intermediates of the 5-hydroxytryptamine (5-HT) biochemical pathway have been measured in the spinal cord of the mouse between 1 day postpartum and adulthood. During the early postnatal period, most components are adult-like or near adult-like, increase to levels greater than the adult by the second week, and return to adult levels thereafter. 5-HT, however, never exceeds adult level and does not attain it until week 4. The early maturation of 5-HT metabolism in the cord is in keeping with the caudal/rostral gradient of maturation in the brain. Possible reasons for this are discussed.

1. 1. Rates of 5-hydroxytryptamine (5-HT) synthesis in hemispheres and brainstem of maturing mouse brain have been made. Inhibitor methods with precursor assay have been employed. 2. 2. Rates of 5-HT synthesis are higher in neonatal brain than in vitro enzyme analysis might suggest. Changes in synthetic rate are more conservative in the hemispheres. The lowest synthetic rates are generally at 1 week of age. 3. 3. The possible general significance of maturational rate patterns for 5-HT synthesis are discussed.

1. 1. Mice either 1 or 7 days old were injected (i.p.) once with LSD in doses of 0·5 μg/kg, 5·0 μg/kg or 50·0 μg/kg, and were then killed for assay at 8 weeks of age. 2. 2. Brains were assayed in four fractions (cerebellum, cerebral hemispheres, mesencephalon-diencephalon, and medulla-pons) for tryptophan-5-hydroxylase (T5-H), 5-hydroxytryptophan decarboxylase (5-HTPD), monoamine oxidase (MAO), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole acetic acid (5-HIAA). 3. 3. Seven day old mice receiving doses of 5·0 μg/kg and 50·0 μg/kg had a 10% elevation of 5-HT in the mesencephalon-diencephalon and a 10% elevation of MAO in the hemispheres. 4. 4. The disruptive action at 7 day exposure correlates with the period of rapid terminal formation by the brain's 5-HT neurons.

1. Mice exposed to LSD on day 1 or day 7 post-partum showed no altered exploratory behavior when tested by the ‘head poke’ test at 8 weeks post-partum. 2. Male mice exposed to LSD (5·0 and 50·0 μ g./kg.) on day 1 post-partum showed reduced brain weight in some regions of the brain when measured at 8 weeks post-partum. Male mice exposed to LSD on day 7 and female mice exposed on day 1 or day 7 showed no such weight change.

1. 1. Levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) were measured in hemispheres and brainstems of maturing mice following monoamine oxidase (MAO) blockade with pargyline. 2. 2. 5-HT elevations were matched by 5-HIAA reduction in 1-, 2- and 6-week-old brains following blockade. 1 Day old brain did not show a 5-HIAA reduction; but did show a 5-HT elevation following blockade. 3. 3. It is suggested that neonatal brain may employ alternative pathway endproducts for 5-HT catabolism.

1. 1. MAO activity was measured in different brain regions of female and male mice of different ages after being treated with testosterone proprionate on day 1, 4 or 7 postpartum. 2. 2. In general, there was an elevation in MAO activity when measured in mice 2 weeks of age or younger and decrease in activity in older mice. 3. 3. Reasons for these results may be related to the maturational state of the indoleamine system and of the different forms of MAO in postnatal development.

1. 1. LSD has been tested in mice to determine whether it causes a change in 5-hydroxytryptamine concentration in eyes, similar to the effect described in brain tissues. 2. 2. No such effect was seen.

1. 1. The larvae of Xenopus laevis, the South African clawed toad, have been assayed for melatonin levels in the lateral eyes, the whole larva and the larva minus eyes. 2. 2. Lateral eyes were found to contain somewhere between 75 to 90 per cent of the total larval melatonin.

1. 5-Hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) stores have been estimated in gerbil cerebral hemispheres and brainstem between one day postpartum and adulthood. 2. Although patterns of 5-HT and 5-HIAA maturation were similar in part to those of the rat and mouse, there was significant difference in the pattern of postnatal 5-HIAA.

1. 1. Mice treated by prenatal injection of pregnant females with LSD or postnatal injection of neonates with LSD or LSD and testosterone were analyzed at various stages of postnatal maturation for changes in brain or body weight or changes in indoleamine levels. 2. 2. LSD caused some variable changes in weight of some brain regions, principally the brain stem and diencephalon of prenatally and postnatally treated mice. Monoamine oxidase levels were elevated in prenatally treated mice. 3. 3. There does not appear to be any clear explanation for these effects of LSD.

1. 1. The effects of parachlorophenylalanine (PCPA), the tryptophan-5-hydroxylase (T5-H) inhibitor, on the maturation of 5-hydroxytryptamine (5-HT) and 5-hydroxy-indole acetic acid (5-HIAA) have been studied in regions of the maturing mouse brain. 2. 2. PCPA does not affect 5-HT levels in 1-day old mice treated on the day of birth, but does decrease it at all subsequent stages studied after 24 hr exposure. 3. 3. 5-HIAA level was unchanged in 1-day old and adult mice treated 24 hr earlier but was lower in almost all brain regions at other stages studied. 4. 4. The results lend support to the hypothesis that the newborn brain is able to synthesize more indoleamine than previously suspected but is unable to store it during the stages of neuronal outgrowth and terminalization.

Monoamine oxidase (MAO) activity and 5-hydroxyindole acetic acid (5-HIAA) amount have been measured in 4 subdivisions of the mouse brain during various stages of postnatal maturation. Each region and each indoleamine pathway component (MAO and 5-HIAA) demonstrated an individual pattern of maturation. MAO increased rapidly from day 1 postpartum and reached adult-like specific activitity by 2 weeks postpartum except in the cerebellum where increase continued after week 6. 5-HIAA levels exceeded adult-like levels by day 3 postpartum, continued to rise during the first week and reached adult level by week 6. Comparison of these data to previously reported maturational patterns of 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan decar☐ylase (5-HTPD), measured upon a similar regional basis, indicate that the components of the indoleamine pathway in the brain do not mature in a harmonious way.

1. At various ages between birth and adulthood mice were exposed to the specific uptake inhibitor citalopram (Lu 10-171) once a day for 5 days. 2. Their brains were assayed for 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) as well as indoleamine turnover at selected times after termination of the drug. 3. Younger brain differed from older brain in both stores and turnover. 4. Younger brain demonstrated the effects of citalopram action as much as 3 weeks later with continued elevation of 5-HIAA stores. 5. The possibility that 5-HIAA is an active agent in serotonergic neurogenesis is discussed.

1. 1. Levels of the intermediates 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) and activities of the enzymes 5-hydroxytryptophan decarboxylase (5-HTPD) and monoamine oxidase (MAO) were measured in 4 different brain regions of maturing mice exposed to LiCl during prenatal and postnatal development. 2. 2. 5-HT and 5-HIAA levels were reduced significantly in all brain regions of 1 day old mice. 5-HIAA was also reduced in hemispheres of 1 week olds. 3. 3. There were some marginally significant elevations and reductions in 5-HTPD and MAO activity at various ages. 4. 4. It is suggested that lithium is reducing 5-HT synthesis and perhaps storage also but that neonates recover quite rapidly from the prenatal exposure.

The effects of tryptophan loading and the acid transport inhibitor, probenecid, on the maturation of 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) have been studied in the maturing mouse brain. Tryptophan loading elevates already high endogenous tryptophan at all stages studied. It does not alter 5-HT or 5-HIAA at day 1 but does elevate levels of both at later stages. Probenecid does not affect 5-HT at any age or 5-HIAA at day 1, but does cause increasingly greater elevations of 5-HIAA at later stages. The results indicate that tryptophan-5-hydroxylase is substrate saturated in early postnatal stages but not later, and that the early postnatal brain lacks an acid transport mechanism for 5-HIAA egress but develops this at later stages.

1. 1. Mice of 1 day, 1 week, 2 weeks, and 6 weeks of age have been injected with the amine depletor reserpine and then measured for changes in body weight, brain weight, and indoleamine stores. 2. 2. Immature mice showed a transient loss of brain weight and a long term loss of body weight. 3. 3. Onset of drug action as reflected in the brains 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) stores was slower in 1 day olds than in later ages. 4. 4. Recovery of 5-HT levels was faster in younger mice while recovery of 5-HIAA levels was faster in older animals. 5. 5. It is suggested that 5-HT recovery is related to differences in 5-HT synthesis at various ages and 5-HIAA recovery is related to the maturity of the brain's acid transport system.

Xenopus larvae raised from stage 21 in melatonin solution and upon a dark background had fewer head melanophores at stage 48 than control animals not exposed to melatonin. Rearing larvae in melatonin solution seems to mimic rearing larvae on a light background.

Summary 5-Hydroxytryptophan decar☐ylase (5-HTPD) activity has been measured in 4 subdivisions of the mouse brain during various stages of postnatal maturation. Each region demonstrated a different pattern of maturation. During the first few days post-partum increases in enzyme activity are slower than increases in tissue weight for all regions studied. However, by the end of the first week all regions are undergoing rapid increases in enzyme activity. Maturation of the enzyme proceeds in a caudal rostral direction, with cerebellum and medulla-pons reaching adult-like status by 2 weeks, mesencephalon-diencephalon by 4 weeks and cerebral hemispheres sometime after 6 weeks. Comparisons of these enzyme data to previously reported data for 5-hydroxytryptamine (5-HT) maturation, measured upon a similar basis, indicate that the enzyme (5-HTPD) and its product (5-HT) mature differently in all regions.

1. 1. Embroyos of Xenopus laevis , the South African clawed toad, have been reared in light-background and dark-background aquaria. At premetamorphic stage (stage 48 of Nieuwkoop and Faber) the embryos were measured in vitro for the indoleamine enzymes 5-hydroxytryptophan decarboxylase (5-HTPD), monoamine oxidase (MAO), an hydroxyindole- O -methyltransferase (HIOMT). Whole embroyo, brain, and lateral eyes were assayed. 2. 2. 5-HTPD activity was lower in whole embryo from light-background aquaria, but was unchanged in brain and eyes. 3. 3. MAO activity was unchanged in whole from light-background aquaria, but was lower in brain and eyes. 4. 4. HIOMT activity was higher in whole embryo from light-background aquaria, but this proved to be the result of HIOMT increase in the brain. Eyes were unchanged.

At various ages between birth and adulthood mice were exposed to the specific 5-HT uptake inhibitor citalopram. Their brains were assayed for indoleamine stores and turnover during the period of recovery from the drug's action. Young brain lacks the ability to fine tune its return to normal following citalopram action.

1. 1. Xenopus laevis embryos were reared in melatonin solutions of 2 μg/ml and 20 μg/ml for periods of 2 hr and 20 hr during stage 48, and between stages 38–48. All larvae were observed for their behavior and some were sectioned for microscopic observation. The enzymes 5-hydroxytryptophan decarboxylase (5-HTPD), monoamine oxidase (MAO) and hydroxyindole- O -methyltransferase (HIOMT) were assayed in whole embryo, brain, eyes and gut. 2. 2. Defecation and gulping occurred in all but control and 2 hr exposed larvae and larvae showing these responses were found to have empty intestines when examined in section under the microscope. 3. 3. Only MAO changed in activity and only in the gut and whole embryo of larvae exposed from stage 38–48. In these larvae the MAO was elevated and dose related.

Eyes from mice have been assayed for 5-HT content at various times during the day. 5-HT levels are highest midway in the light period and lowest during the dark period. In general this daily variation conforms with other published reports for variation of 5-HT stores in brain and pineal.